VCV002599739.3 - ClinVar

NM_001375380.1(EBF3):c.950C>T (p.Pro317Leu)

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.

(2)

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.

Likely benign

criteria provided, single submitter

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_001375380.1(EBF3):c.950C>T (p.Pro317Leu)

Variation ID: 2599739 Accession: VCV002599739.3

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 10q26.3 10: 129867230 (GRCh38) [ NCBI UCSC ] 10: 131665494 (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	Oct 28, 2023	May 1, 2024	Jun 29, 2023

HGVS

Nucleotide	Protein	Molecular consequence
NM_001375380.1:c.950C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001362309.1:p.Pro317Leu	missense
NM_001005463.3:c.923C>T	NP_001005463.1:p.Pro308Leu	missense
NM_001375379.1:c.950C>T	NP_001362308.1:p.Pro317Leu	missense
NM_001375389.1:c.950C>T	NP_001362318.1:p.Pro317Leu	missense
NM_001375390.1:c.923C>T	NP_001362319.1:p.Pro308Leu	missense
NM_001375391.1:c.950C>T	NP_001362320.1:p.Pro317Leu	missense
NM_001375392.1:c.923C>T	NP_001362321.1:p.Pro308Leu	missense
NC_000010.11:g.129867230G>A
NC_000010.10:g.131665494G>A
NG_030038.1:g.101598C>T
NG_121130.1:g.625G>A

... more HGVS ... less HGVS

Protein change

P317L, P308L

Other names

p.P308L

Canonical SPDI

NC_000010.11:129867229:G:A

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.

Links

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.
EBF3		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	241	342

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.
Hypotonia, ataxia, and delayed development syndrome	Uncertain significance (1)	no assertion criteria provided	Jan 18, 2023	RCV003492871.1
Inborn genetic diseases	Likely benign (1)	criteria provided, single submitter	Jun 29, 2023	RCV003345604.2

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.
Likely benign (Jun 29, 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: SCV004066374.2 First in ClinVar: Oct 28, 2023 Last updated: May 01, 2024	Comment: This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of … (more) This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less)
Uncertain significance (Jan 18, 2023)	no assertion criteria provided Method: clinical testing	Hypotonia, ataxia, and delayed development syndrome Affected status: yes Allele origin: de novo	Undiagnosed Diseases Network, NIH Study: Undiagnosed Diseases Network (NIH), UDN Accession: SCV004242192.1 First in ClinVar: Feb 04, 2024 Last updated: Feb 04, 2024	Number of individuals with the variant: 1 Clinical Features: Abnormal electroretinogram (present) , Retinal dystrophy (present) , Nystagmus (present) , Optic atrophy (present) , Cerebellar ataxia (present) , Global developmental delay (present) , Recurrent … (more) Abnormal electroretinogram (present) , Retinal dystrophy (present) , Nystagmus (present) , Optic atrophy (present) , Cerebellar ataxia (present) , Global developmental delay (present) , Recurrent respiratory infections (present) , Decreased circulating antibody level (present) (less) Age: 10-19 years Sex: female Tissue: Blood

Comment:

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

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 this variant ...

Record last updated Jul 15, 2024

ClinVar Genomic variation as it relates to human health

NM_001375380.1(EBF3):c.950C>T (p.Pro317Leu)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...