VCV000854374.7 - ClinVar

NM_145698.5(ACBD5):c.1285G>A (p.Asp429Asn)

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(3)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Uncertain significance

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_145698.5(ACBD5):c.1285G>A (p.Asp429Asn)

Variation ID: 854374 Accession: VCV000854374.7

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 10p12.1 10: 27208365 (GRCh38) [ NCBI UCSC ] 10: 27497294 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Apr 15, 2020	May 1, 2024	Apr 19, 2023

HGVS

Nucleotide	Protein	Molecular consequence
NM_145698.5:c.1285G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_663736.2:p.Asp429Asn	missense
NM_001042473.4:c.1180G>A	NP_001035938.1:p.Asp394Asn	missense
NM_001271512.3:c.1279G>A	NP_001258441.1:p.Asp427Asn	missense
NM_001301251.2:c.958G>A	NP_001288180.1:p.Asp320Asn	missense
NM_001301252.2:c.958G>A	NP_001288181.1:p.Asp320Asn	missense
NM_001301253.2:c.958G>A	NP_001288182.1:p.Asp320Asn	missense
NM_001301254.2:c.754G>A	NP_001288183.1:p.Asp252Asn	missense
NM_001352568.1:c.1339G>A	NP_001339497.1:p.Asp447Asn	missense
NM_001352569.1:c.1318G>A	NP_001339498.1:p.Asp440Asn	missense
NM_001352570.1:c.1285G>A	NP_001339499.1:p.Asp429Asn	missense
NM_001352571.1:c.1312G>A	NP_001339500.1:p.Asp438Asn	missense
NM_001352572.1:c.1306G>A	NP_001339501.1:p.Asp436Asn	missense
NM_001352573.1:c.1264G>A	NP_001339502.1:p.Asp422Asn	missense
NM_001352574.2:c.1213G>A	NP_001339503.1:p.Asp405Asn	missense
NM_001352575.2:c.1213G>A	NP_001339504.1:p.Asp405Asn	missense
NM_001352576.2:c.1213G>A	NP_001339505.1:p.Asp405Asn	missense
NM_001352577.2:c.1180G>A	NP_001339506.1:p.Asp394Asn	missense
NM_001352578.2:c.1180G>A	NP_001339507.1:p.Asp394Asn	missense
NM_001352579.2:c.1180G>A	NP_001339508.1:p.Asp394Asn	missense
NM_001352580.2:c.1126G>A	NP_001339509.1:p.Asp376Asn	missense
NM_001352581.1:c.1114G>A	NP_001339510.1:p.Asp372Asn	missense
NM_001352582.2:c.976G>A	NP_001339511.1:p.Asp326Asn	missense
NM_001352583.1:c.958G>A	NP_001339512.1:p.Asp320Asn	missense
NM_001352584.1:c.958G>A	NP_001339513.1:p.Asp320Asn	missense
NM_001352585.1:c.991G>A	NP_001339514.1:p.Asp331Asn	missense
NM_001352586.1:c.1108G>A	NP_001339515.1:p.Asp370Asn	missense
NM_001352587.1:c.1075G>A	NP_001339516.1:p.Asp359Asn	missense
NM_001352588.1:c.1081G>A	NP_001339517.1:p.Asp361Asn	missense
NM_145698.3:c.1285G>A
NC_000010.11:g.27208365C>T
NC_000010.10:g.27497294C>T
NG_032960.3:g.45310G>A

... more HGVS ... less HGVS

Protein change

D252N, D326N, D370N, D394N, D405N, D422N, D372N, D429N, D438N, D447N, D320N, D331N, D376N, D440N, D359N, D361N, D427N, D436N

Other names

Canonical SPDI

NC_000010.11:27208364:C:T

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

The Genome Aggregation Database (gnomAD), exomes 0.00001

Exome Aggregation Consortium (ExAC) 0.00002

Trans-Omics for Precision Medicine (TOPMed) 0.00003

The Genome Aggregation Database (gnomAD) 0.00006

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00008

Links

dbSNP: rs144860164 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
ACBD5		-	-	GRCh38 GRCh37	355	434

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
not provided	Uncertain significance (1)	criteria provided, single submitter	Oct 17, 2022	RCV001059411.5
Retinal dystrophy with leukodystrophy	not provided (1)	no classification provided	-	RCV001535500.1
Inborn genetic diseases	Uncertain significance (1)	criteria provided, single submitter	Apr 19, 2023	RCV003259071.2

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Uncertain significance (Oct 17, 2022)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV001224035.4 First in ClinVar: Apr 15, 2020 Last updated: Feb 07, 2023	Comment: This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 429 of the ACBD5 protein … (more) This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 429 of the ACBD5 protein (p.Asp429Asn). This variant is present in population databases (rs144860164, gnomAD 0.008%). This variant has not been reported in the literature in individuals affected with ACBD5-related conditions. ClinVar contains an entry for this variant (Variation ID: 854374). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt ACBD5 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. (less)
Uncertain significance (Apr 19, 2023)	criteria provided, single submitter (Ambry Variant Classification Scheme 2023) Method: clinical testing	Inborn genetic diseases Affected status: unknown Allele origin: germline	Ambry Genetics Accession: SCV003973602.2 First in ClinVar: Jul 08, 2023 Last updated: May 01, 2024	Comment: The c.1285G>A (p.D429N) alteration is located in exon 10 (coding exon 10) of the ACBD5 gene. This alteration results from a G to A substitution … (more) The c.1285G>A (p.D429N) alteration is located in exon 10 (coding exon 10) of the ACBD5 gene. This alteration results from a G to A substitution at nucleotide position 1285, causing the aspartic acid (D) at amino acid position 429 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. (less)
not provided (-)	no classification provided Method: phenotyping only	Retinal dystrophy with leukodystrophy Affected status: unknown Allele origin: unknown	GenomeConnect - Invitae Patient Insights Network Accession: SCV001749453.1 First in ClinVar: Jul 18, 2021 Last updated: Jul 18, 2021	Comment: Variant interpreted as Uncertain significance and reported on 11-05-2020 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided … (more) Variant interpreted as Uncertain significance and reported on 11-05-2020 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information. (less) Clinical Features: Abnormality of eye movement (present) , Abnormal lens morphology (present) , Abnormality of vision (present) , Myopia (present) , Abnormal retinal morphology (present) , Depression … (more) Abnormality of eye movement (present) , Abnormal lens morphology (present) , Abnormality of vision (present) , Myopia (present) , Abnormal retinal morphology (present) , Depression (present) (less) Indication for testing: Diagnostic Age: 50-59 years Sex: female Testing laboratory: Invitae Date variant was reported to submitter: 2020-11-05 Testing laboratory interpretation: Uncertain significance

Comment:

This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 429 of the ACBD5 protein (p.Asp429Asn). This variant is present in population databases (rs144860164, gnomAD 0.008%). This variant has not been reported in the literature in individuals affected with ACBD5-related conditions. ClinVar contains an entry for this variant (Variation ID: 854374). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt ACBD5 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

Comment:

The c.1285G>A (p.D429N) alteration is located in exon 10 (coding exon 10) of the ACBD5 gene. This alteration results from a G to A substitution at nucleotide position 1285, causing the aspartic acid (D) at amino acid position 429 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

Comment:

Variant interpreted as Uncertain significance and reported on 11-05-2020 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information.

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Comment:

Citations for germline classification of this variant

There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar.

Text-mined citations for rs144860164 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Sep 29, 2024

ClinVar Genomic variation as it relates to human health

NM_145698.5(ACBD5):c.1285G>A (p.Asp429Asn)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs144860164 ...