rs140513119

Variant names:

• chr5-134968056-C-G
• rs140513119
• NM_178019.3:c.65C>G

Your query was ambiguous. Multiple possible variants found:

• chr5-134968056-C-G
• chr5-134968056-C-T

Variant summary

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

The NM_178019.3(CATSPER3):​c.65C>G​(p.Ser22Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,328 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. S22L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CATSPER3 NM_178019.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.664
• Publications: 0 publications found

Genes affected

CATSPER3 (HGNC:20819): (cation channel sperm associated 3) Predicted to enable voltage-gated calcium channel activity. Predicted to be involved in flagellated sperm motility; sodium ion transport; and sperm capacitation. Predicted to be located in plasma membrane. Predicted to be part of CatSper complex. Predicted to be active in acrosomal vesicle. [provided by Alliance of Genome Resources, Apr 2022]

PCBD2 (HGNC:24474): (pterin-4 alpha-carbinolamine dehydratase 2) Predicted to enable 4-alpha-hydroxytetrahydrobiopterin dehydratase activity. Involved in positive regulation of transcription, DNA-templated. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

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=0.4118687).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178019.3. 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
	CATSPER3	NM_178019.3	MANE Select	c.65C>G	p.Ser22Trp	missense	Exon 1 of 8	NP_821138.1	Q86XQ3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CATSPER3	ENST00000282611.8	TSL:1 MANE Select	c.65C>G	p.Ser22Trp	missense	Exon 1 of 8	ENSP00000282611.6	Q86XQ3
	PCBD2	ENST00000512783.5	TSL:1	c.*3604C>G		3_prime_UTR	Exon 5 of 5	ENSP00000421544.1	Q9H0N5
	CATSPER3	ENST00000511235.1	TSL:4	n.150C>G		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461328 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 727034

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111506

Other (OTH) AF: 0.00 AC: 0 AN: 60376

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Uncertain	0.095	D
BayesDel_noAF	Benign	-0.10
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.094	T
Eigen	Benign	-0.70
Eigen_PC	Benign	-0.84
FATHMM_MKL	Benign	0.068	N
LIST_S2	Benign	0.55	T
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.41	T
MetaSVM	Uncertain	0.24	D
MutationAssessor	Benign	1.1	L
PhyloP100		0.66
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.7	N
REVEL	Uncertain	0.33
Sift	Uncertain	0.011	D
Sift4G	Uncertain	0.039	D
Polyphen		0.99	D
Vest4		0.47
MutPred		0.36		Loss of disorder (P = 0)
MVP		0.69
MPC		0.56
ClinPred		0.34	T
GERP RS		1.8
PromoterAI		0.032	Neutral
Varity_R		0.041
gMVP		0.40
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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: rs140513119; hg19: chr5-134303746;