19-38346459-C-G

Variant names:

• chr19-38346459-C-G
• rs193036151
• NM_021185.5:c.679C>G

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.679C>G​(p.Leu227Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000197 in 152,118 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.000020 (0 hom., cov: 32)
• Consequence: CATSPERG NM_021185.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.239
• 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=0.13339856).

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.679C>G	p.Leu227Val	missense	Exon 7 of 29	NP_067008.3
	CATSPERG	NM_001330496.2		c.679C>G	p.Leu227Val	missense	Exon 7 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.679C>G	p.Leu227Val	missense	Exon 7 of 29	ENSP00000386962.3	Q6ZRH7
	CATSPERG	ENST00000409410.6	TSL:1	c.679C>G	p.Leu227Val	missense	Exon 7 of 17	ENSP00000386950.2	X1WI24
	CATSPERG	ENST00000412458.6	TSL:1	n.268C>G		non_coding_transcript_exon	Exon 4 of 26	ENSP00000395093.2	F8WDD6

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152118 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152118 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74302

African (AFR) AF: 0.0000724 AC: 3 AN: 41418

American (AMR) AF: 0.00 AC: 0 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	9.5
DANN	Uncertain	0.99
DEOGEN2	Benign	0.025	T
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.056	N
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.5	L
PhyloP100		-0.24
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.11
Sift	Uncertain	0.0080	D
Sift4G	Benign	0.14	T
Polyphen		1.0	D
Vest4		0.20
MutPred		0.24		Loss of stability (P = 0.1272)
MVP		0.16
MPC		0.52
ClinPred		0.16	T
GERP RS		-1.4
Varity_R		0.096
gMVP		0.27
Mutation Taster		=99/1	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: rs193036151; hg19: chr19-38837099;