Genetic Variant CATSPER3:p.Asp206Ala (chr5-135008081-A-C) – 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_178019.3(CATSPER3):c.617A>C(p.Asp206Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000125 in 1,614,134 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00072 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000062 ( 0 hom. )

Consequence

CATSPER3
NM_178019.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.76

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:

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=0.1084744).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CATSPER3	NM_178019.3 link	c.617A>C	p.Asp206Ala	missense_variant	Exon 4 of 8	ENST00000282611.8	NP_821138.1	Q86XQ3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CATSPER3	ENST00000282611.8 link	c.617A>C	p.Asp206Ala	missense_variant	Exon 4 of 8	1	NM_178019.3	ENSP00000282611.6		Q86XQ3
PCBD2	ENST00000504352.1 link	n.*723A>C		downstream_gene_variant		5		ENSP00000426161.1		H0YA52

Frequencies

GnomAD3 genomes

AF:

0.000716

AC:

109

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

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:

0.000478

GnomAD3 exomes

AF:

0.000179

AC:

AN:

251458

Hom.:

AF XY:

0.000162

AC XY:

AN XY:

135912

show subpopulations

Gnomad AFR exome

AF:

0.00209

Gnomad AMR exome

AF:

0.000289

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:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000622

AC:

AN:

1461866

Hom.:

Cov.:

AF XY:

0.0000550

AC XY:

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.00218

Gnomad4 AMR exome

AF:

0.000268

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:

0.0000993

GnomAD4 genome

AF:

0.000722

AC:

110

AN:

152268

Hom.:

Cov.:

AF XY:

0.000712

AC XY:

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.00243

Gnomad4 AMR

AF:

0.000458

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:

0.000473

Alfa

AF:

0.000119

Hom.:

Bravo

AF:

0.000895

ESP6500AA

AF:

0.00227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000198

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 06, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.617A>C (p.D206A) alteration is located in exon 4 (coding exon 4) of the CATSPER3 gene. This alteration results from a A to C substitution at nucleotide position 617, causing the aspartic acid (D) at amino acid position 206 to be replaced by an alanine (A). 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

0.76

BayesDel_addAF

Benign

-0.059

BayesDel_noAF

Pathogenic

0.14

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.54

Eigen

Benign

0.13

Eigen_PC

Benign

-0.054

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.49

M_CAP

Uncertain

0.17

MetaRNN

Benign

0.11

MetaSVM

Pathogenic

0.83

MutationAssessor

Pathogenic

3.1

PrimateAI

Benign

0.43

PROVEAN

Uncertain

-3.0

REVEL

Uncertain

0.59

Sift

Uncertain

0.0070

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.47

MVP

0.88

MPC

0.55

ClinPred

0.16

GERP RS

3.2

Varity_R

0.28

gMVP

0.89

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