Variant 14-91591996-C-T 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_024764.4(CATSPERB):c.2716G>A(p.Gly906Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000963 in 1,608,928 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000091 ( 0 hom. )

Consequence

CATSPERB
NM_024764.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.55

Variant links:

Genes affected

CATSPERB (HGNC:20500): (cation channel sperm associated auxiliary subunit beta) Predicted to be involved in cell differentiation and spermatogenesis. Predicted to be located in plasma membrane. Predicted to be part of CatSper complex. Predicted to be active in cilium. [provided by Alliance of Genome Resources, Apr 2022]

CATSPERB 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=0.07657516).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CATSPERB	NM_024764.4 linkuse as main transcript	c.2716G>A	p.Gly906Ser	missense_variant	23/27	ENST00000256343.8	NP_079040.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CATSPERB	ENST00000256343.8 linkuse as main transcript	c.2716G>A	p.Gly906Ser	missense_variant	23/27	1	NM_024764.4	ENSP00000256343	P1	Q9H7T0-1
CATSPERB	ENST00000556429.1 linkuse as main transcript	n.557G>A		non_coding_transcript_exon_variant	1/2	3
CATSPERB	ENST00000557036.1 linkuse as main transcript	c.*1197G>A		3_prime_UTR_variant, NMD_transcript_variant	9/13	2		ENSP00000451083

Frequencies

GnomAD3 genomes

AF:

0.000151

AC:

AN:

152094

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00519

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000131

AC:

AN:

250968

Hom.:

AF XY:

0.0000958

AC XY:

AN XY:

135654

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00169

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000984

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000106

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000906

AC:

132

AN:

1456834

Hom.:

Cov.:

AF XY:

0.000101

AC XY:

AN XY:

725062

show subpopulations

Gnomad4 AFR exome

AF:

0.0000599

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00176

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000163

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000524

Gnomad4 OTH exome

AF:

0.000183

GnomAD4 genome

AF:

0.000151

AC:

AN:

152094

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74304

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00519

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000181

Hom.:

Bravo

AF:

0.000113

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.0000988

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000119

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 04, 2021

The c.2716G>A (p.G906S) alteration is located in exon 23 (coding exon 22) of the CATSPERB gene. This alteration results from a G to A substitution at nucleotide position 2716, causing the glycine (G) at amino acid position 906 to be replaced by a serine (S). 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

Uncertain

0.48

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.40

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.25

Eigen

Uncertain

0.43

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Benign

0.62

M_CAP

Benign

0.027

MetaRNN

Benign

0.077

MetaSVM

Benign

-0.81

MutationAssessor

Uncertain

2.8

MutationTaster

Benign

0.96

PrimateAI

Benign

0.44

PROVEAN

Uncertain

-3.9

REVEL

Benign

0.10

Sift

Benign

0.094

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.48

MVP

0.70

MPC

0.80

ClinPred

0.91

GERP RS

4.3

Varity_R

0.21

gMVP

0.62

Splicing

Name

Calibrated prediction

Score

Prediction

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

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