chr19-38360801-T-C

Variant names:

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

Variant summary

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

The NM_021185.5(CATSPERG):​c.1838T>C​(p.Met613Thr) 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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CATSPERG NM_021185.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.091296345).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CATSPERG	NM_021185.5	c.1838T>C	p.Met613Thr	missense_variant	Exon 16 of 29	ENST00000409235.8	NP_067008.3
CATSPERG	NM_001330496.2	c.1718T>C	p.Met573Thr	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>C	p.Met613Thr	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

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 11, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1838T>C (p.M613T) alteration is located in exon 16 (coding exon 15) of the CATSPERG gene. This alteration results from a T to C substitution at nucleotide position 1838, causing the methionine (M) at amino acid position 613 to be replaced by a threonine (T). 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	0.23
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	4.9
DANN	Benign	0.36
DEOGEN2	Benign	0.017	.;T;.
Eigen	Benign	-0.79
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.062	N
LIST_S2	Benign	0.61	T;T;T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.091	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	.;L;.
PhyloP100		0.085
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.1	N;N;N
REVEL	Benign	0.020
Sift	Benign	0.41	T;T;T
Sift4G	Benign	0.37	T;T;T
Polyphen		0.55	P;B;.
Vest4		0.42
MutPred		0.36		.;Loss of helix (P = 0.0167);Loss of helix (P = 0.0167);
MVP		0.16
MPC		0.30
ClinPred		0.062	T
GERP RS		1.3
Varity_R		0.055
gMVP		0.36
Mutation Taster		=94/6	polymorphism

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

Other links and lift over

dbSNP: rs1970331645; hg19: chr19-38851441;