rs299362

Positions:

• chr5-134985856-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_178019.3(CATSPER3):​c.253-10417G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.921 in 151,768 control chromosomes in the GnomAD database, including 64,463 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.92 (64463 hom., cov: 28)
• Consequence: CATSPER3 NM_178019.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.858

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]

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]

CATSPER3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.964 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CATSPER3	NM_178019.3	c.253-10417G>A		intron_variant		ENST00000282611.8	NP_821138.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CATSPER3	ENST00000282611.8	c.253-10417G>A		intron_variant		1	NM_178019.3	ENSP00000282611.6
PCBD2	ENST00000504352.1	n.*359-10417G>A		intron_variant		5		ENSP00000426161.1
CATSPER3	ENST00000511235.1	n.338-9785G>A		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.921 AC: 139636 AN: 151650 Hom.: 64410 Cov.: 28

Gnomad AFR AF: 0.972

Gnomad AMI AF: 0.964

Gnomad AMR AF: 0.932

Gnomad ASJ AF: 0.892

Gnomad EAS AF: 0.884

Gnomad SAS AF: 0.863

Gnomad FIN AF: 0.967

Gnomad MID AF: 0.921

Gnomad NFE AF: 0.888

Gnomad OTH AF: 0.916

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.921 AC: 139745 AN: 151768 Hom.: 64463 Cov.: 28 AF XY: 0.924 AC XY: 68486 AN XY: 74116

Gnomad4 AFR AF: 0.972

Gnomad4 AMR AF: 0.932

Gnomad4 ASJ AF: 0.892

Gnomad4 EAS AF: 0.883

Gnomad4 SAS AF: 0.863

Gnomad4 FIN AF: 0.967

Gnomad4 NFE AF: 0.888

Gnomad4 OTH AF: 0.913

Alfa AF: 0.908 Hom.: 12289

Bravo AF: 0.922

Asia WGS AF: 0.897 AC: 3116 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.43
DANN	Benign	0.14

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

Other links and lift over

dbSNP: rs299362; hg19: chr5-134321546;