19-38343681-G-C

Variant names:

• chr19-38343681-G-C
• NM_021185.5:c.426G>C
• CATSPERG p.Glu142Asp

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.426G>C​(p.Glu142Asp) 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. 13/22 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: CATSPERG NM_021185.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.200
• 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=0.1789763).

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.426G>C	p.Glu142Asp	missense	Exon 4 of 29	NP_067008.3
	CATSPERG	NM_001330496.2		c.426G>C	p.Glu142Asp	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.426G>C	p.Glu142Asp	missense	Exon 4 of 29	ENSP00000386962.3	Q6ZRH7
	CATSPERG	ENST00000409410.6	TSL:1	c.426G>C	p.Glu142Asp	missense	Exon 4 of 17	ENSP00000386950.2	X1WI24
	CATSPERG	ENST00000412458.6	TSL:1	n.15G>C		non_coding_transcript_exon	Exon 1 of 26	ENSP00000395093.2	F8WDD6

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.58
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	15
DANN	Uncertain	1.0
DEOGEN2	Benign	0.044	T
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.55
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.0078	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		-0.20
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.17
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Varity_R		0.47
gMVP		0.35
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr19-38834321;