chr1-26190752-C-T

Variant names:

• chr1-26190752-C-T
• rs144361455
• NM_198137.2:c.125C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_198137.2(CATSPER4):​c.125C>T​(p.Pro42Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,324 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P42R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: CATSPER4 NM_198137.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.584
• Publications: 1 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]

ENSG00000302380 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11504704).

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.125C>T	p.Pro42Leu	missense	Exon 1 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.125C>T	p.Pro42Leu	missense	Exon 1 of 10	ENSP00000390423.3	Q7RTX7-1
	CATSPER4	ENST00000518899.5	TSL:1	n.125C>T		non_coding_transcript_exon	Exon 1 of 10	ENSP00000429464.1	Q7RTX7-2
	CATSPER4	ENST00000338855.6	TSL:5	c.125C>T	p.Pro42Leu	missense	Exon 1 of 9	ENSP00000341006.2	J3KNU1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000401 AC: 1 AN: 249328 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000888

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000547 AC: 8 AN: 1461324 Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4 AN XY: 726904

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44654

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26116

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86144

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53228

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 0.00000540 AC: 6 AN: 1111894

Other (OTH) AF: 0.0000166 AC: 1 AN: 60362

GnomAD4 genome Cov.: 31

Alfa AF: 0.0000434 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.023	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	7.7
DANN	Uncertain	0.98
DEOGEN2	Benign	0.049	T
Eigen	Benign	-0.86
Eigen_PC	Benign	-0.88
FATHMM_MKL	Benign	0.057	N
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.059	D
MetaRNN	Benign	0.12	T
MetaSVM	Uncertain	0.12	D
MutationAssessor	Benign	1.1	L
PhyloP100		-0.58
PrimateAI	Benign	0.29	T
PROVEAN	Benign	0.21	N
REVEL	Benign	0.096
Sift	Benign	0.059	T
Sift4G	Uncertain	0.016	D
Polyphen		0.063	B
Vest4		0.19
MutPred		0.38		Gain of helix (P = 0.0034)
MVP		0.55
MPC		0.18
ClinPred		0.074	T
GERP RS		2.4
PromoterAI		0.0078	Neutral
Varity_R		0.023
gMVP		0.23
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.19		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: rs144361455; hg19: chr1-26517243;