Variant 1-26197743-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_198137.2(CATSPER4):c.517A>T(p.Ile173Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,740 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: 0.0000041 ( 0 hom. )

Consequence

CATSPER4
NM_198137.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.596

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.27245647).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CATSPER4	NM_198137.2 linkuse as main transcript	c.517A>T	p.Ile173Phe	missense_variant	4/10	ENST00000456354.7	NP_937770.1	Q7RTX7-1
CATSPER4	XM_011541432.4 linkuse as main transcript	c.517A>T	p.Ile173Phe	missense_variant	4/9		XP_011539734.1
CATSPER4	XM_011541433.3 linkuse as main transcript	c.517A>T	p.Ile173Phe	missense_variant	4/7		XP_011539735.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CATSPER4	ENST00000456354.7 linkuse as main transcript	c.517A>T	p.Ile173Phe	missense_variant	4/10	1	NM_198137.2	ENSP00000390423.3	Q7RTX7-1
CATSPER4	ENST00000518899.5 linkuse as main transcript	n.517A>T		non_coding_transcript_exon_variant	4/10	1		ENSP00000429464.1	Q7RTX7-2
CATSPER4	ENST00000338855.6 linkuse as main transcript	c.517A>T	p.Ile173Phe	missense_variant	4/9	5		ENSP00000341006.2	J3KNU1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000410

AC:

AN:

1461740

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727168

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:

0.00000450

Gnomad4 OTH exome

AF:

0.0000166

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

Feb 06, 2024

The c.517A>T (p.I173F) alteration is located in exon 4 (coding exon 4) of the CATSPER4 gene. This alteration results from a A to T substitution at nucleotide position 517, causing the isoleucine (I) at amino acid position 173 to be replaced by a phenylalanine (F). 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

0.067

BayesDel_addAF

Benign

-0.0038

BayesDel_noAF

Benign

-0.24

CADD

Benign

0.044

DANN

Benign

0.53

DEOGEN2

Uncertain

0.50

.;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0087

LIST_S2

Benign

0.58

T;T

M_CAP

Benign

0.027

MetaRNN

Benign

0.27

T;T

MetaSVM

Uncertain

0.072

MutationAssessor

Benign

0.21

.;N

MutationTaster

Benign

1.0

PrimateAI

Benign

0.43

PROVEAN

Benign

-1.1

N;N

REVEL

Uncertain

0.34

Sift

Benign

0.21

T;T

Sift4G

Benign

0.21

T;T

Polyphen

0.026

.;B

Vest4

0.20

MutPred

0.70

Loss of catalytic residue at I173 (P = 0.0801);Loss of catalytic residue at I173 (P = 0.0801);

MVP

0.39

MPC

0.28

ClinPred

0.081

GERP RS

-1.5

Varity_R

0.099

gMVP

0.87

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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