Variant 14-91587275-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The ENST00000256343.8(CATSPERB):c.3059G>T(p.Gly1020Val) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000069 in 1,449,416 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

CATSPERB
ENST00000256343.8 missense, splice_region

Scores

Splicing: ADA: 0.3880

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.94

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.837

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CATSPERB	NM_024764.4 linkuse as main transcript	c.3059G>T	p.Gly1020Val	missense_variant, splice_region_variant	26/27	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.3059G>T	p.Gly1020Val	missense_variant, splice_region_variant	26/27	1	NM_024764.4	ENSP00000256343.3	Q9H7T0-1
CATSPERB	ENST00000557036.1 linkuse as main transcript	n.*1540G>T		splice_region_variant, non_coding_transcript_exon_variant	12/13	2		ENSP00000451083.1	H0YJA5
CATSPERB	ENST00000557036.1 linkuse as main transcript	n.*1540G>T		3_prime_UTR_variant	12/13	2		ENSP00000451083.1	H0YJA5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.90e-7

AC:

AN:

1449416

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

720958

show subpopulations

Gnomad4 AFR exome

AF:

0.0000308

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Oct 20, 2021

The c.3059G>T (p.G1020V) alteration is located in exon 26 (coding exon 25) of the CATSPERB gene. This alteration results from a G to T substitution at nucleotide position 3059, causing the glycine (G) at amino acid position 1020 to be replaced by a valine (V). 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

Pathogenic

0.91

BayesDel_addAF

Pathogenic

0.32

BayesDel_noAF

Pathogenic

0.23

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.31

Eigen

Uncertain

0.61

Eigen_PC

Uncertain

0.55

FATHMM_MKL

Uncertain

0.92

M_CAP

Uncertain

0.26

MetaRNN

Pathogenic

0.84

MetaSVM

Uncertain

0.14

MutationAssessor

Uncertain

2.8

MutationTaster

Benign

1.0

PrimateAI

Benign

0.47

PROVEAN

Pathogenic

-7.4

REVEL

Uncertain

0.57

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.88

MutPred

0.49

Gain of catalytic residue at L1023 (P = 0.0082);

MVP

0.87

MPC

0.90

ClinPred

1.0

GERP RS

5.6

Varity_R

0.92

gMVP

0.82

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.39

dbscSNV1_RF

Benign

0.49

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over