NM_178019.3:c.16C>T

Variant names:

• chr5-134968007-C-T
• rs1370415252
• NM_178019.3:c.16C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_178019.3(CATSPER3):​c.16C>T​(p.His6Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,622 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CATSPER3 NM_178019.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0320
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08531365).

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.16C>T	p.His6Tyr	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.16C>T	p.His6Tyr	missense	Exon 1 of 8	ENSP00000282611.6	Q86XQ3
	PCBD2	ENST00000512783.5	TSL:1	c.*3555C>T		3_prime_UTR	Exon 5 of 5	ENSP00000421544.1	Q9H0N5
	CATSPER3	ENST00000511235.1	TSL:4	n.101C>T		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251416 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461622 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 727146

African (AFR) AF: 0.00 AC: 0 AN: 33476

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

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86240

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111784

Other (OTH) AF: 0.00 AC: 0 AN: 60386

GnomAD4 genome Cov.: 32

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	0.063
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	0.44
DANN	Benign	0.84
DEOGEN2	Benign	0.069	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.026	N
LIST_S2	Benign	0.35	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.085	T
MetaSVM	Uncertain	-0.12	T
MutationAssessor	Benign	0.34	N
PhyloP100		-0.032
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.46	N
REVEL	Benign	0.18
Sift	Uncertain	0.012	D
Sift4G	Uncertain	0.031	D
Polyphen		0.0	B
Vest4		0.051
MutPred		0.29		Loss of helix (P = 0.0558)
MVP		0.42
MPC		0.11
ClinPred		0.046	T
GERP RS		-5.2
PromoterAI		-0.018	Neutral
Varity_R		0.039
gMVP		0.34
Mutation Taster		=100/0	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: rs1370415252; hg19: chr5-134303697;