11-66017182-T-G

Position:

• chr11-66017182-T-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_053054.4(CATSPER1):​c.2202-8A>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.057 (0 hom., cov: 0)
  • Exomes 𝑓: 0.14 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CATSPER1 NM_053054.4 splice_region, intron
• Scores: Splicing: ADA: 0.00001266
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -3.09

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 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CATSPER1	NM_053054.4	c.2202-8A>C		splice_region_variant, intron_variant		ENST00000312106.6	NP_444282.3
CATSPER1	XM_047426337.1	c.*36-8A>C		splice_region_variant, intron_variant			XP_047282293.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CATSPER1	ENST00000312106.6	c.2202-8A>C		splice_region_variant, intron_variant		1	NM_053054.4	ENSP00000309052.5
CATSPER1	ENST00000529244.1	n.442-8A>C		splice_region_variant, intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.00 AC: 542 AN: 9476 Hom.: 0 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.0577

Gnomad AMI AF: 0.0278

Gnomad AMR AF: 0.0330

Gnomad ASJ AF: 0.0588

Gnomad EAS AF: 0.0238

Gnomad SAS AF: 0.0457

Gnomad FIN AF: 0.0277

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0702

Gnomad OTH AF: 0.0694

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.135 AC: 21203 AN: 156888 Hom.: 0 Cov.: 0 AF XY: 0.129 AC XY: 11693 AN XY: 90756

Gnomad4 AFR exome AF: 0.0984

Gnomad4 AMR exome AF: 0.0896

Gnomad4 ASJ exome AF: 0.0845

Gnomad4 EAS exome AF: 0.0640

Gnomad4 SAS exome AF: 0.171

Gnomad4 FIN exome AF: 0.0750

Gnomad4 NFE exome AF: 0.147

Gnomad4 OTH exome AF: 0.160

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0570 AC: 542 AN: 9516 Hom.: 0 Cov.: 0 AF XY: 0.0469 AC XY: 243 AN XY: 5186

Gnomad4 AFR AF: 0.0572

Gnomad4 AMR AF: 0.0328

Gnomad4 ASJ AF: 0.0588

Gnomad4 EAS AF: 0.0239

Gnomad4 SAS AF: 0.0457

Gnomad4 FIN AF: 0.0277

Gnomad4 NFE AF: 0.0701

Gnomad4 OTH AF: 0.0649

Alfa AF: 0.0127 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Spermatogenic failure 7 Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.083
DANN	Benign	0.34

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000013
dbscSNV1_RF	Benign	0.0040
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs1326391621; hg19: chr11-65784653;