Variant 14-91589610-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_024764.4(CATSPERB):c.2880G>C(p.Glu960Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000401 in 1,613,858 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 0.00053 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00039 ( 0 hom. )

Consequence

CATSPERB
NM_024764.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.14

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0043842196).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CATSPERB	NM_024764.4 linkuse as main transcript	c.2880G>C	p.Glu960Asp	missense_variant	24/27	ENST00000256343.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CATSPERB	ENST00000256343.8 linkuse as main transcript	c.2880G>C	p.Glu960Asp	missense_variant	24/27	1	NM_024764.4	P1	Q9H7T0-1
CATSPERB	ENST00000556429.1 linkuse as main transcript	n.721G>C		non_coding_transcript_exon_variant	2/2	3
CATSPERB	ENST00000557036.1 linkuse as main transcript	c.*1361G>C		3_prime_UTR_variant, NMD_transcript_variant	10/13	2

Frequencies

GnomAD3 genomes

AF:

0.000526

AC:

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00327

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000323

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000533

AC:

134

AN:

251354

Hom.:

AF XY:

0.000552

AC XY:

AN XY:

135864

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.00197

Gnomad ASJ exome

AF:

0.0000993

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000449

Gnomad OTH exome

AF:

0.00180

GnomAD4 exome

AF:

0.000388

AC:

567

AN:

1461544

Hom.:

Cov.:

AF XY:

0.000393

AC XY:

286

AN XY:

727108

show subpopulations

Gnomad4 AFR exome

AF:

0.000119

Gnomad4 AMR exome

AF:

0.00188

Gnomad4 ASJ exome

AF:

0.000230

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000395

Gnomad4 OTH exome

AF:

0.000546

GnomAD4 genome

AF:

0.000525

AC:

AN:

152314

Hom.:

Cov.:

AF XY:

0.000631

AC XY:

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.0000962

Gnomad4 AMR

AF:

0.00327

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.000323

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.000354

Hom.:

Bravo

AF:

0.000582

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.000371

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000273

EpiControl

AF:

0.000356

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

Jun 18, 2021

The c.2880G>C (p.E960D) alteration is located in exon 24 (coding exon 23) of the CATSPERB gene. This alteration results from a G to C substitution at nucleotide position 2880, causing the glutamic acid (E) at amino acid position 960 to be replaced by an aspartic acid (D). 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

0.18

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.69

CADD

Benign

3.4

DANN

Uncertain

0.98

DEOGEN2

Benign

0.028

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.017

M_CAP

Benign

0.016

MetaRNN

Benign

0.0044

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

MutationTaster

Benign

1.0

PrimateAI

Benign

0.34

PROVEAN

Benign

-1.3

REVEL

Benign

0.012

Sift

Benign

0.30

Sift4G

Benign

0.091

Polyphen

0.015

Vest4

0.11

MutPred

0.42

Gain of catalytic residue at R963 (P = 0);

MVP

0.19

MPC

0.43

ClinPred

0.010

GERP RS

-3.1

Varity_R

0.050

gMVP

0.30

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