VCV002499993.1 - ClinVar

NM_001386993.1(CTCFL):c.1159C>T (p.Arg387Cys)

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.

(1)

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, single submitter

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_001386993.1(CTCFL):c.1159C>T (p.Arg387Cys)

Variation ID: 2499993 Accession: VCV002499993.1

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 20q13.31 20: 57515735 (GRCh38) [ NCBI UCSC ] 20: 56090791 (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 30, 2023	Apr 30, 2023	Apr 21, 2023

HGVS

Nucleotide	Protein	Molecular consequence
NM_001386993.1:c.1159C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001373922.1:p.Arg387Cys	missense
NM_001269040.2:c.1159C>T	NP_001255969.1:p.Arg387Cys	missense
NM_001269041.2:c.1159C>T	NP_001255970.1:p.Arg387Cys	missense
NM_001269042.2:c.1159C>T	NP_001255971.1:p.Arg387Cys	missense
NM_001269043.2:c.1159C>T	NP_001255972.1:p.Arg387Cys	missense
NM_001269044.3:c.1159C>T	NP_001255973.1:p.Arg387Cys	missense
NM_001269045.2:c.1159C>T	NP_001255974.1:p.Arg387Cys	missense
NM_001269046.2:c.1159C>T	NP_001255975.1:p.Arg387Cys	missense
NM_001269047.2:c.1159C>T	NP_001255976.1:p.Arg387Cys	missense
NM_001269048.3:c.1059+3023C>T		intron variant
NM_001269049.2:c.544C>T	NP_001255978.1:p.Arg182Cys	missense
NM_001269050.3:c.544C>T	NP_001255979.1:p.Arg182Cys	missense
NM_001269054.2:c.373C>T	NP_001255983.1:p.Arg125Cys	missense
NM_001269055.3:c.373C>T	NP_001255984.1:p.Arg125Cys	missense
NM_001386994.1:c.1159C>T	NP_001373923.1:p.Arg387Cys	missense
NM_001386995.1:c.1159C>T	NP_001373924.1:p.Arg387Cys	missense
NM_001386997.1:c.1159C>T	NP_001373926.1:p.Arg387Cys	missense
NM_080618.4:c.1159C>T	NP_542185.2:p.Arg387Cys	missense
NR_072975.3:n.1651C>T		non-coding transcript variant
NR_170377.1:n.1651C>T		non-coding transcript variant
NC_000020.11:g.57515735G>A
NC_000020.10:g.56090791G>A

... more HGVS ... less HGVS

Protein change

R125C, R182C, R387C

Other names

p.Arg387Cys

Canonical SPDI

NC_000020.11:57515734: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.
CTCFL		-	-	GRCh38 GRCh37	56	73

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.
See cases	Uncertain significance (1)	criteria provided, single submitter	Apr 21, 2023	RCV003224083.2

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 (Apr 21, 2023)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	See cases (Autosomal recessive inheritance) Affected status: yes Allele origin: germline	Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics Accession: SCV003918900.1 First in ClinVar: Apr 30, 2023 Last updated: Apr 30, 2023	Comment: A homozygous missense variation in exon 6 of the CTCFL gene that results in the amino acid substitution of Cystine for Arginine at codon 387 … (more) A homozygous missense variation in exon 6 of the CTCFL gene that results in the amino acid substitution of Cystine for Arginine at codon 387 was detected. The variant c.1159C>T (p.Arg387Cys) was not observed in the 1000 genomes and gnomAD databases. The in silico prediction of the variant is damaging by SIFT, DANN, PROVEAN and MetaRNN. The variant was also observed in heterozygous state in unaffected father.In summary, the variant meets our criteria to be classified as a variant of uncertain significance. (less) Clinical Features: Abnormal sperm motility (present) , Oligospermia (present) , Abnormal sperm morphology (present) Age: 30-39 years Method: Germline DNA from peripheral blood was used to perform targeted gene capture using Twist Biosciences Human Core Exome capture kit. Library was sequenced to mean >80-100x coverage on Illumina sequencing platform. We follow GATK’s Best Practices workflow framework for data analysis and variant calling. Sequences obtained were aligned to human reference genome (GRCh38/ hg38) using BWA. Gene annotation is performed either with Variant effect predictor or JANNOVAR. Variant filtration and prioritisation was either performed manually or using Exomiser v13 using available phenotype information translated in HPO terminologies. In addition to SNVs and small indels, copy number variants (CNVs) are detected using ExomeDepth v1.1.10 or GATK gCNV method. Sensitivity of this assay to detect large deletions/ duplications of more than 10bp or CNVs is 70-75%.

Comment:

A homozygous missense variation in exon 6 of the CTCFL gene that results in the amino acid substitution of Cystine for Arginine at codon 387 was detected. The variant c.1159C>T (p.Arg387Cys) was not observed in the 1000 genomes and gnomAD databases. The in silico prediction of the variant is damaging by SIFT, DANN, PROVEAN and MetaRNN. The variant was also observed in heterozygous state in unaffected father.In summary, the variant meets our criteria to be classified as a variant of uncertain significance.

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 Jun 23, 2024

ClinVar Genomic variation as it relates to human health

NM_001386993.1(CTCFL):c.1159C>T (p.Arg387Cys)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...