Genetic Variant CATSPERG:p.Ser272Cys (chr19-38346595-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_021185.5(CATSPERG):c.815C>G(p.Ser272Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000005 in 1,398,840 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000050 ( 0 hom. )

Consequence

CATSPERG
NM_021185.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.328

Variant links:

Genes affected

CATSPERG (HGNC:25243): (cation channel sperm associated auxiliary subunit gamma) CATSPERG is a subunit of the CATSPER (see CATSPER1; MIM 606389) sperm calcium channel, which is required for sperm hyperactivated motility and male fertility (Wang et al., 2009 [PubMed 19516020]).[supplied by OMIM, Jul 2010]

CATSPERG 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=0.13337961).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CATSPERG	NM_021185.5 link	c.815C>G	p.Ser272Cys	missense_variant	Exon 7 of 29	ENST00000409235.8	NP_067008.3	Q6ZRH7Q32MQ2
CATSPERG	NM_001330496.2 link	c.815C>G	p.Ser272Cys	missense_variant	Exon 7 of 28		NP_001317425.1	B8ZZI7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CATSPERG	ENST00000409235.8 link	c.815C>G	p.Ser272Cys	missense_variant	Exon 7 of 29	5	NM_021185.5	ENSP00000386962.3		Q6ZRH7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000640

AC:

AN:

156356

Hom.:

AF XY:

0.0000121

AC XY:

AN XY:

82886

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000165

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000500

AC:

AN:

1398840

Hom.:

Cov.:

AF XY:

0.00000580

AC XY:

AN XY:

689870

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000556

Gnomad4 OTH exome

AF:

0.0000172

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 02, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.815C>G (p.S272C) alteration is located in exon 7 (coding exon 6) of the CATSPERG gene. This alteration results from a C to G substitution at nucleotide position 815, causing the serine (S) at amino acid position 272 to be replaced by a cysteine (C). 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

0.16

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.027

.;T;.

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.63

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.78

T;T;T

M_CAP

Benign

0.022

MetaRNN

Benign

0.13

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

.;L;.

PrimateAI

Benign

0.36

PROVEAN

Benign

-2.0

N;N;N

REVEL

Benign

0.081

Sift

Benign

0.069

T;T;T

Sift4G

Benign

0.062

T;T;T

Polyphen

0.97

D;D;.

Vest4

0.32

MutPred

0.37

Gain of sheet (P = 0.039);Gain of sheet (P = 0.039);Gain of sheet (P = 0.039);

MVP

0.15

MPC

0.70

ClinPred

0.19

GERP RS

0.56

Varity_R

0.077

gMVP

0.36

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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