rs299362

Variant names:

• chr5-134985856-G-A
• rs299362
• NM_178019.3:c.253-10417G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178019.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CATSPER3	NM_178019.3	MANE Select	c.253-10417G>A		intron	N/A	NP_821138.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CATSPER3	ENST00000282611.8	TSL:1 MANE Select	c.253-10417G>A		intron	N/A	ENSP00000282611.6
	PCBD2	ENST00000504352.1	TSL:5	n.*359-10417G>A		intron	N/A	ENSP00000426161.1
	CATSPER3	ENST00000511235.1	TSL:4	n.338-9785G>A		intron	N/A

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

African (AFR) AF: 0.972 AC: 40216 AN: 41364

American (AMR) AF: 0.932 AC: 14201 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.892 AC: 3097 AN: 3472

East Asian (EAS) AF: 0.883 AC: 4495 AN: 5088

South Asian (SAS) AF: 0.863 AC: 4128 AN: 4784

European-Finnish (FIN) AF: 0.967 AC: 10166 AN: 10516

Middle Eastern (MID) AF: 0.915 AC: 269 AN: 294

European-Non Finnish (NFE) AF: 0.888 AC: 60374 AN: 67996

Other (OTH) AF: 0.913 AC: 1922 AN: 2106

Alfa AF: 0.904 Hom.: 16875

Bravo AF: 0.922

Asia WGS AF: 0.897 AC: 3116 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.43
DANN	Benign	0.14
PhyloP100		-0.86
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs299362; hg19: chr5-134321546;