19-38343710-C-T

Variant names:

• chr19-38343710-C-T
• rs1460163898
• NM_021185.5:c.455C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_021185.5(CATSPERG):​c.455C>T​(p.Pro152Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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. P152R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: CATSPERG NM_021185.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.56
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35712898).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021185.5. 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
	CATSPERG	NM_021185.5	MANE Select	c.455C>T	p.Pro152Leu	missense	Exon 4 of 29	NP_067008.3
	CATSPERG	NM_001330496.2		c.455C>T	p.Pro152Leu	missense	Exon 4 of 28	NP_001317425.1	B8ZZI7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CATSPERG	ENST00000409235.8	TSL:5 MANE Select	c.455C>T	p.Pro152Leu	missense	Exon 4 of 29	ENSP00000386962.3	Q6ZRH7
	CATSPERG	ENST00000409410.6	TSL:1	c.455C>T	p.Pro152Leu	missense	Exon 4 of 17	ENSP00000386950.2	X1WI24
	CATSPERG	ENST00000412458.6	TSL:1	n.44C>T		non_coding_transcript_exon	Exon 1 of 26	ENSP00000395093.2	F8WDD6

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.53
BayesDel_addAF	Benign	0.0062	T
BayesDel_noAF	Benign	-0.23
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.055	D
MetaRNN	Benign	0.36	T
MetaSVM	Benign	-0.62	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		4.6
PrimateAI	Benign	0.46	T
PROVEAN	Pathogenic	-5.1	D
REVEL	Benign	0.16
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.69
MutPred		0.33		Gain of helix (P = 6e-04)
MVP		0.35
MPC		0.73
ClinPred		1.0	D
GERP RS		5.0
Varity_R		0.58
gMVP		0.63
Mutation Taster		=82/18	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: rs1460163898; hg19: chr19-38834350; COSMIC: COSV53047532; COSMIC: COSV53047532;