19-38360801-T-G

Variant names:

• chr19-38360801-T-G
• rs1970331645
• NM_021185.5:c.1838T>G

Variant summary

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

The NM_021185.5(CATSPERG):​c.1838T>G​(p.Met613Arg) 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. 14/24 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. M613T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CATSPERG NM_021185.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0850
• Publications: 0 publications found

Genes affected

CATSPERG (HGNC:25243): (cation channel sperm associated auxiliary subunit gamma) CATSPERG is a subunit of the CATSPER (see CATSPER1; MIM 606389) sperm calcium channel, which is required for sperm hyperactivated motility and male fertility (Wang et al., 2009 [PubMed 19516020]).[supplied by OMIM, Jul 2010]

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CATSPERG	NM_021185.5	c.1838T>G	p.Met613Arg	missense_variant	Exon 16 of 29	ENST00000409235.8	NP_067008.3
CATSPERG	NM_001330496.2	c.1718T>G	p.Met573Arg	missense_variant	Exon 15 of 28		NP_001317425.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CATSPERG	ENST00000409235.8	c.1838T>G	p.Met613Arg	missense_variant	Exon 16 of 29	5	NM_021185.5	ENSP00000386962.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	20
DANN	Benign	0.82
DEOGEN2	Benign	0.044	.;T;.
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.094	N
LIST_S2	Benign	0.66	T;T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.13	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	.;M;.
PhyloP100		0.085
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-2.2	N;N;N
REVEL	Benign	0.13
Sift	Benign	0.083	T;D;D
Sift4G	Uncertain	0.045	D;D;T
Polyphen		0.74	P;B;.
Vest4		0.54
MutPred		0.40		.;Gain of solvent accessibility (P = 0.0584);Gain of solvent accessibility (P = 0.0584);
MVP		0.18
MPC		0.38
ClinPred		0.12	T
GERP RS		1.3
Varity_R		0.25
gMVP		0.58
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.80		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.80		Position offset: 0

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

Other links and lift over

dbSNP: rs1970331645; hg19: chr19-38851441;