Variant 1-244572425-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PM1PM2BP4_Strong

The NM_001130957.2(CATSPERE):c.1603A>C(p.Asn535His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000454 in 1,606,760 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000050 ( 1 hom. )

Consequence

CATSPERE
NM_001130957.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.725

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 Uncertain_significance. Variant got 0 ACMG points.

PM1

In a glycosylation_site N-linked (GlcNAc...) asparagine (size 0) in uniprot entity CTSRE_HUMAN

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06735158).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CATSPERE	NM_001130957.2 linkuse as main transcript	c.1603A>C	p.Asn535His	missense_variant	11/22	ENST00000366534.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CATSPERE	ENST00000366534.9 linkuse as main transcript	c.1603A>C	p.Asn535His	missense_variant	11/22	2	NM_001130957.2	P2	Q5SY80-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000557

AC:

AN:

251142

Hom.:

AF XY:

0.0000442

AC XY:

AN XY:

135760

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000360

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000881

Gnomad OTH exome

AF:

0.000327

GnomAD4 exome

AF:

0.0000495

AC:

AN:

1454536

Hom.:

Cov.:

AF XY:

0.0000525

AC XY:

AN XY:

724064

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000616

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000118

Gnomad4 OTH exome

AF:

0.0000665

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152224

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000312

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.0000577

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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

Jul 16, 2021

The c.1603A>C (p.N535H) alteration is located in exon 11 (coding exon 11) of the C1orf101 gene. This alteration results from a A to C substitution at nucleotide position 1603, causing the asparagine (N) at amino acid position 535 to be replaced by a histidine (H). 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

0.17

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.66

CADD

Benign

9.0

DANN

Benign

0.97

DEOGEN2

Benign

0.010

.;T;.;.

Eigen

Benign

-0.87

Eigen_PC

Benign

-0.89

FATHMM_MKL

Benign

0.054

LIST_S2

Benign

0.68

T;T;T;T

M_CAP

Benign

0.0064

MetaRNN

Benign

0.067

T;T;T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

N;N;N

PROVEAN

Uncertain

-2.4

N;N;N;N

REVEL

Benign

0.10

Sift

Benign

0.18

T;T;T;T

Sift4G

Benign

0.25

T;T;D;T

Polyphen

0.21, 0.83

.;B;B;P

Vest4

0.15

MutPred

0.43

.;Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);.;

MVP

0.13

MPC

0.27

ClinPred

0.19

GERP RS

4.1

Varity_R

0.068

gMVP

0.49

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