1-26193865-A-G

Position:

• chr1-26193865-A-G

Variant summary

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

The NM_198137.2(CATSPER4):​c.436A>G​(p.Asn146Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CATSPER4 NM_198137.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.61

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CATSPER4	NM_198137.2	c.436A>G	p.Asn146Asp	missense_variant	3/10	ENST00000456354.7	NP_937770.1
CATSPER4	XM_011541432.4	c.436A>G	p.Asn146Asp	missense_variant	3/9		XP_011539734.1
CATSPER4	XM_011541433.3	c.436A>G	p.Asn146Asp	missense_variant	3/7		XP_011539735.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CATSPER4	ENST00000456354.7	c.436A>G	p.Asn146Asp	missense_variant	3/10	1	NM_198137.2	ENSP00000390423	P1
CATSPER4	ENST00000518899.5	c.436A>G	p.Asn146Asp	missense_variant, NMD_transcript_variant	3/10	1		ENSP00000429464
CATSPER4	ENST00000338855.6	c.436A>G	p.Asn146Asp	missense_variant	3/9	5		ENSP00000341006

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

Nov 16, 2021

The c.436A>G (p.N146D) alteration is located in exon 3 (coding exon 3) of the CATSPER4 gene. This alteration results from a A to G substitution at nucleotide position 436, causing the asparagine (N) at amino acid position 146 to be replaced by an aspartic acid (D). 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	0.20
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.030
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.56	.;D
Eigen	Benign	0.18
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.72	T;T
M_CAP	Uncertain	0.094	D
MetaRNN	Uncertain	0.47	T;T
MetaSVM	Uncertain	0.46	D
MutationAssessor	Benign	1.2	.;L
MutationTaster	Benign	0.75	N
PrimateAI	Uncertain	0.48	T
PROVEAN	Benign	-1.4	N;N
REVEL	Uncertain	0.47
Sift	Benign	0.42	T;T
Sift4G	Benign	0.12	T;T
Polyphen		0.96	.;D
Vest4		0.38
MutPred		0.68		Gain of relative solvent accessibility (P = 0.0479);Gain of relative solvent accessibility (P = 0.0479);
MVP		0.90
MPC		0.50
ClinPred		0.93	D
GERP RS		5.0
Varity_R		0.24
gMVP		0.89

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-26520356;