Variant 11-66017080-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_053054.4(CATSPER1):c.2296A>G(p.Ile766Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,594 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CATSPER1
NM_053054.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.996

Variant links:

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 links:

CATSPER1 (HGNC:):

CATSPER1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.19041303).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CATSPER1	NM_053054.4 linkuse as main transcript	c.2296A>G	p.Ile766Val	missense_variant	11/12	ENST00000312106.6	NP_444282.3	Q8NEC5
CATSPER1	XM_047426337.1 linkuse as main transcript	c.*130A>G		downstream_gene_variant			XP_047282293.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CATSPER1	ENST00000312106.6 linkuse as main transcript	c.2296A>G	p.Ile766Val	missense_variant	11/12	1	NM_053054.4	ENSP00000309052.5		Q8NEC5
CATSPER1	ENST00000529244.1 linkuse as main transcript	n.536A>G		non_coding_transcript_exon_variant	5/6	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461594

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727100

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 12, 2021

The c.2296A>G (p.I766V) alteration is located in exon 11 (coding exon 11) of the CATSPER1 gene. This alteration results from a A to G substitution at nucleotide position 2296, causing the isoleucine (I) at amino acid position 766 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Uncertain

0.046

BayesDel_noAF

Benign

-0.17

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.061

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.47

FATHMM_MKL

Benign

0.51

LIST_S2

Benign

0.60

M_CAP

Benign

0.058

MetaRNN

Benign

0.19

MetaSVM

Uncertain

0.12

MutationAssessor

Benign

1.5

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.50

REVEL

Benign

0.20

Sift

Benign

0.056

Sift4G

Uncertain

0.031

Polyphen

0.38

Vest4

0.28

MutPred

0.31

Loss of helix (P = 0.0376);

MVP

0.83

MPC

0.34

ClinPred

0.12

GERP RS

1.8

Varity_R

0.037

gMVP

0.095

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.18

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over