1-26197734-C-A

Variant names:

• chr1-26197734-C-A
• rs144083626
• NM_198137.2:c.508C>A

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_198137.2(CATSPER4):​c.508C>A​(p.Arg170Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000821 in 1,461,592 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000082 (0 hom.)
• Consequence: CATSPER4 NM_198137.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.808
• Publications: 3 publications found

Genes affected

CATSPER4 (HGNC:23220): (cation channel sperm associated 4) 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 and sperm principal piece. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198137.2. 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
	CATSPER4	NM_198137.2	MANE Select	c.508C>A	p.Arg170Arg	synonymous	Exon 4 of 10	NP_937770.1	Q7RTX7-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CATSPER4	ENST00000456354.7	TSL:1 MANE Select	c.508C>A	p.Arg170Arg	synonymous	Exon 4 of 10	ENSP00000390423.3	Q7RTX7-1
	CATSPER4	ENST00000518899.5	TSL:1	n.508C>A		non_coding_transcript_exon	Exon 4 of 10	ENSP00000429464.1	Q7RTX7-2
	CATSPER4	ENST00000338855.6	TSL:5	c.508C>A	p.Arg170Arg	synonymous	Exon 4 of 9	ENSP00000341006.2	J3KNU1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000821 AC: 12 AN: 1461592 Hom.: 0 Cov.: 32 AF XY: 0.0000124 AC XY: 9 AN XY: 727090

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86242

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5600

European-Non Finnish (NFE) AF: 0.0000108 AC: 12 AN: 1111932

Other (OTH) AF: 0.00 AC: 0 AN: 60370

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	14
DANN	Benign	0.45
PhyloP100		0.81
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.55		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.55		Position offset: 2
DS_AL_spliceai		0.26		Position offset: -48

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs144083626; hg19: chr1-26524225;