rs193929391

Variant names:

• chr11-66025431-C-CGCCAT
• rs193929391
• NM_053054.4:c.944_948dupATGGC

Variant summary

Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_053054.4(CATSPER1):​c.944_948dupATGGC​(p.Asp317MetfsTer20) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 30)
• Consequence: CATSPER1 NM_053054.4 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1 O:1
• Conservation: PhyloP100: -4.70
• Publications: 11 publications found

Genes affected

CATSPER1 (HGNC:17116): (cation channel sperm associated 1) Calcium ions play a primary role in the regulation of sperm motility. This gene belongs to a family of putative cation channels that are specific to spermatozoa and localize to the flagellum. The protein family features a single repeat with six membrane-spanning segments and a predicted calcium-selective pore region. [provided by RefSeq, Jul 2008]

CATSPER1 Gene-Disease associations (from GenCC):

• non-syndromic male infertility due to sperm motility disorder

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• spermatogenic failure 7

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Pathogenic. The variant received 11 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 11-66025431-C-CGCCAT is Pathogenic according to our data. Variant chr11-66025431-C-CGCCAT is described in ClinVar as Pathogenic. ClinVar VariationId is 4401.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CATSPER1	NM_053054.4	c.944_948dupATGGC	p.Asp317MetfsTer20	frameshift_variant	Exon 1 of 12	ENST00000312106.6	NP_444282.3
CATSPER1	XM_047426337.1	c.944_948dupATGGC	p.Asp317MetfsTer20	frameshift_variant	Exon 1 of 11		XP_047282293.1
CATSPER1	XM_047426338.1	c.944_948dupATGGC	p.Asp317MetfsTer20	frameshift_variant	Exon 1 of 6		XP_047282294.1
CATSPER1	XR_002957121.2	n.1044_1048dupATGGC		non_coding_transcript_exon_variant	Exon 1 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CATSPER1	ENST00000312106.6	c.944_948dupATGGC	p.Asp317MetfsTer20	frameshift_variant	Exon 1 of 12	1	NM_053054.4	ENSP00000309052.5

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 30

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1 Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Spermatogenic failure 7 Pathogenic:1 Other:1

-

GeneReviews

Significance: not provided

Review Status: no classification provided

Collection Method: literature only

- -

Apr 01, 2009

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-4.7
Mutation Taster		=120/80	disease causing (ClinVar)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs193929391; hg19: chr11-65792902;