VCV002443913.1 - ClinVar

NM_001304548.2(CFAP47):c.[1337C>T;706G>A]

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.

Pathogenic

no assertion criteria provided

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

This haplotype includes the following variants

NM_001304548.2(CFAP47):c.[1337C>T;706G>A]

Other names: CFAP47, VAL236MET AND THR446MET
Functional consequence: -
Links: OMIM: 301057.0004

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.
CFAP47		-	-	GRCh38 GRCh37	46	206

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.
Spermatogenic failure, X-linked, 3	Pathogenic (1)	no assertion criteria provided	Mar 10, 2023	RCV003152521.2

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.
Pathogenic (Mar 10, 2023)	no assertion criteria provided Method: literature only	SPERMATOGENIC FAILURE, X-LINKED, 3 Affected status: not provided Allele origin: germline	OMIM Accession: SCV003841115.1 First in ClinVar: Mar 18, 2023 Last updated: Mar 18, 2023	Publications: PubMed (1) PubMed: 36571501 Comment on evidence: In a Chinese man with infertility due to multiple morphologic abnormalities of the flagella (SPGFX3; 301059), Liao et al. (2022) identified hemizygosity for 2 mutations … (more) In a Chinese man with infertility due to multiple morphologic abnormalities of the flagella (SPGFX3; 301059), Liao et al. (2022) identified hemizygosity for 2 mutations in the CFAP47 gene: a c.706G-A transition (c.706G-A, NM_001304548.2) in exon 5 resulting in a val236-to-met (V236M) substitution, and a c.1337C-T transition (c.1337C-T, NM_001304548.2) in exon 8 resulting in a thr446-to-met (V446M) substitution. Both substitutions involved conserved residues, and neither was found in the 1000 Genomes Project or gnomAD databases. Parental mutation status was not reported. Western blot showed a dramatic decrease in CFAP47 in patient sperm compared to fertile controls. The authors demonstrated that CFAP47 interacts with WDR87 (620274) in the middle piece of spermatozoa flagella in mouse and human. Patient sperm showed significantly reduced expression of the 100-kD WDR87 isoform that predominates in sperm, with only a weak WDR87 signal adjacent to the nucleus detected, suggesting that WDR87 transport to the flagellar midpiece requires CFAP47. (less)

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.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
WDR87 interacts with CFAP47 protein in the middle piece of spermatozoa flagella to participate in sperm tail assembly.	Liao HQ	Molecular human reproduction	2022	PMID: 36571501

Text-mined citations for this variant ...

Record last updated Jan 26, 2024

ClinVar Genomic variation as it relates to human health

NM_001304548.2(CFAP47):c.[1337C>T;706G>A]

Variant Details

NM_001304548.2(CFAP47):c.[1337C>T;706G>A]

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...