19-38344070-C-A

Variant names:

• chr19-38344070-C-A
• rs375537032
• NM_021185.5:c.547C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_021185.5(CATSPERG):​c.547C>A​(p.Arg183Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,399,328 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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. R183H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: CATSPERG NM_021185.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.72
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0365583).

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.547C>A	p.Arg183Ser	missense	Exon 5 of 29	NP_067008.3
	CATSPERG	NM_001330496.2		c.547C>A	p.Arg183Ser	missense	Exon 5 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.547C>A	p.Arg183Ser	missense	Exon 5 of 29	ENSP00000386962.3	Q6ZRH7
	CATSPERG	ENST00000409410.6	TSL:1	c.547C>A	p.Arg183Ser	missense	Exon 5 of 17	ENSP00000386950.2	X1WI24
	CATSPERG	ENST00000412458.6	TSL:1	n.136C>A		non_coding_transcript_exon	Exon 2 of 26	ENSP00000395093.2	F8WDD6

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1399328 Hom.: 0 Cov.: 32 AF XY: 0.00000145 AC XY: 1 AN XY: 690176

African (AFR) AF: 0.00 AC: 0 AN: 31592

American (AMR) AF: 0.00 AC: 0 AN: 35702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25178

East Asian (EAS) AF: 0.00 AC: 0 AN: 35736

South Asian (SAS) AF: 0.00 AC: 0 AN: 79222

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49298

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5684

European-Non Finnish (NFE) AF: 9.27e-7 AC: 1 AN: 1078906

Other (OTH) AF: 0.00 AC: 0 AN: 58010

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.091	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	0.11
DANN	Benign	0.71
DEOGEN2	Benign	0.015	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.0093	N
LIST_S2	Benign	0.41	T
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.037	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L
PhyloP100		-1.7
PrimateAI	Benign	0.20	T
PROVEAN	Benign	-0.87	N
REVEL	Uncertain	0.32
Sift	Benign	0.93	T
Sift4G	Benign	0.67	T
Polyphen		0.0	B
Vest4		0.16
MutPred		0.44		Loss of MoRF binding (P = 0.0296)
MVP		0.030
MPC		0.25
ClinPred		0.049	T
GERP RS		-9.5
Varity_R		0.088
gMVP		0.37
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs375537032; hg19: chr19-38834710;