Variant chr5-134968004-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_178019.3(CATSPER3):c.13C>T(p.Arg5Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000855 in 1,613,662 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00036 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000057 ( 1 hom. )

Consequence

CATSPER3
NM_178019.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.06

Variant links:

Genes affected

CATSPER3 (HGNC:20819): (cation channel sperm associated 3) Predicted to enable voltage-gated calcium channel activity. Predicted to be involved in flagellated sperm motility; sodium ion transport; and sperm capacitation. Predicted to be located in plasma membrane. Predicted to be part of CatSper complex. Predicted to be active in acrosomal vesicle. [provided by Alliance of Genome Resources, Apr 2022]

CATSPER3 links:

PCBD2 (HGNC:24474): (pterin-4 alpha-carbinolamine dehydratase 2) Predicted to enable 4-alpha-hydroxytetrahydrobiopterin dehydratase activity. Involved in positive regulation of transcription, DNA-templated. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

PCBD2 links:

CATSPER3 (HGNC:):

CATSPER3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.016904056).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CATSPER3	NM_178019.3 linkuse as main transcript	c.13C>T	p.Arg5Cys	missense_variant	1/8	ENST00000282611.8	NP_821138.1	Q86XQ3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CATSPER3	ENST00000282611.8 linkuse as main transcript	c.13C>T	p.Arg5Cys	missense_variant	1/8	1	NM_178019.3	ENSP00000282611.6	Q86XQ3
PCBD2	ENST00000512783.5 linkuse as main transcript	c.*3552C>T		3_prime_UTR_variant	5/5	1		ENSP00000421544.1	Q9H0N5
CATSPER3	ENST00000511235.1 linkuse as main transcript	n.98C>T		non_coding_transcript_exon_variant	1/3	4
PCBD2	ENST00000504352.1 linkuse as main transcript	n.*18-1935C>T		intron_variant		5		ENSP00000426161.1	H0YA52

Frequencies

GnomAD3 genomes

AF:

0.000362

AC:

AN:

152112

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00118

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

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:

0.000955

GnomAD3 exomes

AF:

0.000103

AC:

AN:

251398

Hom.:

AF XY:

0.0000662

AC XY:

AN XY:

135866

show subpopulations

Gnomad AFR exome

AF:

0.00105

Gnomad AMR exome

AF:

0.000202

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:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000568

AC:

AN:

1461432

Hom.:

Cov.:

AF XY:

0.0000509

AC XY:

AN XY:

727044

show subpopulations

Gnomad4 AFR exome

AF:

0.00105

Gnomad4 AMR exome

AF:

0.000179

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000171

Gnomad4 OTH exome

AF:

0.000331

GnomAD4 genome

AF:

0.000361

AC:

AN:

152230

Hom.:

Cov.:

AF XY:

0.000430

AC XY:

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.00118

Gnomad4 AMR

AF:

0.000196

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:

0.000945

Alfa

AF:

0.0000681

Hom.:

Bravo

AF:

0.000457

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000123

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

Jul 07, 2024

The c.13C>T (p.R5C) alteration is located in exon 1 (coding exon 1) of the CATSPER3 gene. This alteration results from a C to T substitution at nucleotide position 13, causing the arginine (R) at amino acid position 5 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

0.088

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.27

CADD

Benign

1.8

DANN

Benign

0.86

DEOGEN2

Benign

0.028

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.00077

LIST_S2

Benign

0.53

M_CAP

Benign

0.012

MetaRNN

Benign

0.017

MetaSVM

Uncertain

0.20

MutationAssessor

Benign

0.69

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.15

REVEL

Uncertain

0.34

Sift

Benign

0.17

Sift4G

Benign

0.12

Polyphen

0.92

Vest4

0.12

MVP

0.41

MPC

0.19

ClinPred

0.023

GERP RS

-5.4

Varity_R

0.041

gMVP

0.27

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