Variant chr14-91621619-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.2249G>A(p.Arg750Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000264 in 1,588,412 control chromosomes in the GnomAD database, including 1 homozygotes. 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 0.000046 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000024 ( 1 hom. )

Consequence

CATSPERB
NM_024764.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.92

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=0.07281858).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CATSPERB	NM_024764.4 linkuse as main transcript	c.2249G>A	p.Arg750Gln	missense_variant	19/27	ENST00000256343.8	NP_079040.2	Q9H7T0-1B3KWW9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CATSPERB	ENST00000256343.8 linkuse as main transcript	c.2249G>A	p.Arg750Gln	missense_variant	19/27	1	NM_024764.4	ENSP00000256343.3	Q9H7T0-1
CATSPERB	ENST00000557036.1 linkuse as main transcript	n.*730G>A		non_coding_transcript_exon_variant	5/13	2		ENSP00000451083.1	H0YJA5
CATSPERB	ENST00000557036.1 linkuse as main transcript	n.*730G>A		3_prime_UTR_variant	5/13	2		ENSP00000451083.1	H0YJA5

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000638

AC:

AN:

235216

Hom.:

AF XY:

0.0000628

AC XY:

AN XY:

127364

show subpopulations

Gnomad AFR exome

AF:

0.0000626

Gnomad AMR exome

AF:

0.0000325

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000449

Gnomad SAS exome

AF:

0.0000727

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000277

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000244

AC:

AN:

1436292

Hom.:

Cov.:

AF XY:

0.0000266

AC XY:

AN XY:

713140

show subpopulations

Gnomad4 AFR exome

AF:

0.0000618

Gnomad4 AMR exome

AF:

0.0000248

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000152

Gnomad4 SAS exome

AF:

0.0000483

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000164

Gnomad4 OTH exome

AF:

0.0000169

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152120

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74304

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000627

Hom.:

Bravo

AF:

0.0000416

ExAC

AF:

0.0000494

AC:

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 30, 2021

The c.2249G>A (p.R750Q) alteration is located in exon 19 (coding exon 18) of the CATSPERB gene. This alteration results from a G to A substitution at nucleotide position 2249, causing the arginine (R) at amino acid position 750 to be replaced by a glutamine (Q). 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

0.082

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.68

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.021

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.50

FATHMM_MKL

Benign

0.34

M_CAP

Benign

0.016

MetaRNN

Benign

0.073

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.69

MutationTaster

Benign

1.0

PrimateAI

Benign

0.31

PROVEAN

Benign

0.47

REVEL

Benign

0.10

Sift

Benign

0.38

Sift4G

Benign

0.20

Polyphen

0.86

Vest4

0.038

MutPred

0.43

Gain of catalytic residue at V748 (P = 0.0101);

MVP

0.33

MPC

0.24

ClinPred

0.046

GERP RS

3.6

Varity_R

0.033

gMVP

0.57

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