Variant 1-26191417-C-G 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_198137.2(CATSPER4):c.344C>G(p.Ser115Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000159 in 1,614,216 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00017 ( 0 hom. )

Consequence

CATSPER4
NM_198137.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.136

Variant links:

Genes affected

CATSPER4 (HGNC:23220): (cation channel sperm associated 4) Predicted to enable voltage-gated calcium channel activity. Predicted to be involved in flagellated sperm motility; sodium ion transport; and sperm capacitation. Predicted to be located in plasma membrane. Predicted to be part of CatSper complex. Predicted to be active in acrosomal vesicle and sperm principal piece. [provided by Alliance of Genome Resources, Apr 2022]

CATSPER4 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=0.17990005).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CATSPER4	NM_198137.2 link	c.344C>G	p.Ser115Cys	missense_variant	2/10	ENST00000456354.7	NP_937770.1	Q7RTX7-1
CATSPER4	XM_011541432.4 link	c.344C>G	p.Ser115Cys	missense_variant	2/9		XP_011539734.1
CATSPER4	XM_011541433.3 link	c.344C>G	p.Ser115Cys	missense_variant	2/7		XP_011539735.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CATSPER4	ENST00000456354.7 link	c.344C>G	p.Ser115Cys	missense_variant	2/10	1	NM_198137.2	ENSP00000390423.3	Q7RTX7-1
CATSPER4	ENST00000518899.5 link	n.344C>G		non_coding_transcript_exon_variant	2/10	1		ENSP00000429464.1	Q7RTX7-2
CATSPER4	ENST00000338855.6 link	c.344C>G	p.Ser115Cys	missense_variant	2/9	5		ENSP00000341006.2	J3KNU1

Frequencies

GnomAD3 genomes

AF:

0.0000328

AC:

AN:

152250

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000131

AC:

AN:

251208

Hom.:

AF XY:

0.000110

AC XY:

AN XY:

135804

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000185

Gnomad NFE exome

AF:

0.000229

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.000172

AC:

252

AN:

1461848

Hom.:

Cov.:

AF XY:

0.000164

AC XY:

119

AN XY:

727224

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:

0.000112

Gnomad4 NFE exome

AF:

0.000209

Gnomad4 OTH exome

AF:

0.000232

GnomAD4 genome

AF:

0.0000328

AC:

AN:

152368

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74512

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.0000793

Hom.:

Bravo

AF:

0.0000680

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000189

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

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

Aug 20, 2024

The c.344C>G (p.S115C) alteration is located in exon 2 (coding exon 2) of the CATSPER4 gene. This alteration results from a C to G substitution at nucleotide position 344, causing the serine (S) at amino acid position 115 to be replaced by a cysteine (C). 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

0.13

BayesDel_addAF

Benign

-0.076

BayesDel_noAF

Uncertain

-0.060

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Uncertain

0.79

.;D

Eigen

Benign

-0.17

Eigen_PC

Benign

-0.33

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.67

T;T

M_CAP

Benign

0.057

MetaRNN

Benign

0.18

T;T

MetaSVM

Uncertain

0.38

MutationAssessor

Benign

2.0

.;M

PrimateAI

Benign

0.36

PROVEAN

Benign

-2.2

N;N

REVEL

Uncertain

0.41

Sift

Benign

0.20

T;T

Sift4G

Uncertain

0.039

D;D

Polyphen

1.0

.;D

Vest4

0.35

MVP

0.86

MPC

0.51

ClinPred

0.082

GERP RS

1.3

Varity_R

0.18

gMVP

0.64

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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