Variant chr1-244640068-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001130957.2(CATSPERE):c.2843G>A(p.Arg948His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00059 in 1,548,230 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00043 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00061 ( 1 hom. )

Consequence

CATSPERE
NM_001130957.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.315

Variant links:

Genes affected

CATSPERE (HGNC:28491): (catsper channel auxiliary subunit epsilon) Located in sperm principal piece. [provided by Alliance of Genome Resources, Apr 2022]

CATSPERE links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.011717528).

BP6

Variant 1-244640068-G-A is Benign according to our data. Variant chr1-244640068-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3137821.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CATSPERE	NM_001130957.2 linkuse as main transcript	c.2843G>A	p.Arg948His	missense_variant	22/22	ENST00000366534.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CATSPERE	ENST00000366534.9 linkuse as main transcript	c.2843G>A	p.Arg948His	missense_variant	22/22	2	NM_001130957.2	P2	Q5SY80-1

Frequencies

GnomAD3 genomes

AF:

0.000427

AC:

AN:

152108

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000459

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000632

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000284

AC:

AN:

154684

Hom.:

AF XY:

0.000317

AC XY:

AN XY:

81954

show subpopulations

Gnomad AFR exome

AF:

0.000126

Gnomad AMR exome

AF:

0.0000832

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000134

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000614

Gnomad OTH exome

AF:

0.000229

GnomAD4 exome

AF:

0.000607

AC:

848

AN:

1396004

Hom.:

Cov.:

AF XY:

0.000629

AC XY:

433

AN XY:

688620

show subpopulations

Gnomad4 AFR exome

AF:

0.000382

Gnomad4 AMR exome

AF:

0.000199

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000216

Gnomad4 FIN exome

AF:

0.0000407

Gnomad4 NFE exome

AF:

0.000732

Gnomad4 OTH exome

AF:

0.000328

GnomAD4 genome

AF:

0.000427

AC:

AN:

152226

Hom.:

Cov.:

AF XY:

0.000430

AC XY:

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.000457

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000632

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000357

Hom.:

Bravo

AF:

0.000336

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00126

AC:

ExAC

AF:

0.000365

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 02, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.80

CADD

Benign

5.4

DANN

Benign

0.30

DEOGEN2

Benign

0.017

.;T;.

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.0016

LIST_S2

Benign

0.43

T;T;T

M_CAP

Benign

0.0027

MetaRNN

Benign

0.012

T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N;N

PROVEAN

Benign

-0.98

N;N;N

REVEL

Benign

0.0070

Sift

Benign

0.38

T;T;T

Sift4G

Benign

0.29

T;T;T

Polyphen

0.0020

.;B;B

Vest4

0.022

MVP

0.040

MPC

0.20

ClinPred

0.0031

GERP RS

-4.6

Varity_R

0.020

gMVP

0.061

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