1-26190775-C-T

Position:

• chr1-26190775-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_198137.2(CATSPER4):​c.148C>T​(p.His50Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: CATSPER4 NM_198137.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0610

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

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=0.09357342).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CATSPER4	NM_198137.2	c.148C>T	p.His50Tyr	missense_variant	1/10	ENST00000456354.7	NP_937770.1
CATSPER4	XM_011541432.4	c.148C>T	p.His50Tyr	missense_variant	1/9		XP_011539734.1
CATSPER4	XM_011541433.3	c.148C>T	p.His50Tyr	missense_variant	1/7		XP_011539735.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CATSPER4	ENST00000456354.7	c.148C>T	p.His50Tyr	missense_variant	1/10	1	NM_198137.2	ENSP00000390423.3
CATSPER4	ENST00000518899.5	n.148C>T		non_coding_transcript_exon_variant	1/10	1		ENSP00000429464.1
CATSPER4	ENST00000338855.6	c.148C>T	p.His50Tyr	missense_variant	1/9	5		ENSP00000341006.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 22, 2024

The c.148C>T (p.H50Y) alteration is located in exon 1 (coding exon 1) of the CATSPER4 gene. This alteration results from a C to T substitution at nucleotide position 148, causing the histidine (H) at amino acid position 50 to be replaced by a tyrosine (Y). 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	0.080
BayesDel_addAF	Benign	-0.077	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	3.0
DANN	Benign	0.91
DEOGEN2	Benign	0.045	.;T
Eigen	Benign	-0.97
Eigen_PC	Benign	-0.98
FATHMM_MKL	Benign	0.055	N
LIST_S2	Benign	0.53	T;T
M_CAP	Benign	0.039	D
MetaRNN	Benign	0.094	T;T
MetaSVM	Uncertain	-0.036	T
MutationAssessor	Benign	0.64	.;N
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.13	N;N
REVEL	Benign	0.15
Sift	Benign	0.34	T;T
Sift4G	Benign	0.42	T;T
Polyphen		0.0010	.;B
Vest4		0.16
MutPred		0.31		Gain of sheet (P = 0.0125);Gain of sheet (P = 0.0125);
MVP		0.72
MPC		0.20
ClinPred		0.16	T
GERP RS		1.6
Varity_R		0.040
gMVP		0.46

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: rs267598522; hg19: chr1-26517266; COSMIC: COSV58794155; COSMIC: COSV58794155;