rs2484173

Positions:

• chr10-27399065-A-G
• chr10-27399065-A-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001034842.5(PTCHD3):​c.1533T>C​(p.Ser511=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.656 in 1,609,400 control chromosomes in the GnomAD database, including 353,605 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.62 (29815 hom., cov: 30)
  • Exomes 𝑓: 0.66 (323790 hom.)
• Consequence: PTCHD3 NM_001034842.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.09

Genes affected

PTCHD3 (HGNC:24776): (patched domain containing 3 (gene/pseudogene)) Predicted to be located in sperm midpiece. Predicted to be active in membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP7: Synonymous conserved (PhyloP=-2.09 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.673 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTCHD3	NM_001034842.5	c.1533T>C	p.Ser511=	synonymous_variant	4/4		NP_001030014.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTCHD3	ENST00000642324.1	c.1533T>C	p.Ser511=	synonymous_variant	4/4			ENSP00000495205	P1

Frequencies

GnomAD3 genomes AF: 0.622 AC: 94262 AN: 151644 Hom.: 29785 Cov.: 30

Gnomad AFR AF: 0.548

Gnomad AMI AF: 0.746

Gnomad AMR AF: 0.562

Gnomad ASJ AF: 0.749

Gnomad EAS AF: 0.342

Gnomad SAS AF: 0.664

Gnomad FIN AF: 0.687

Gnomad MID AF: 0.704

Gnomad NFE AF: 0.678

Gnomad OTH AF: 0.643

GnomAD3 exomes AF: 0.615 AC: 154404 AN: 251090 Hom.: 49656 AF XY: 0.631 AC XY: 85592 AN XY: 135712

Gnomad AFR exome AF: 0.545

Gnomad AMR exome AF: 0.429

Gnomad ASJ exome AF: 0.748

Gnomad EAS exome AF: 0.350

Gnomad SAS exome AF: 0.696

Gnomad FIN exome AF: 0.679

Gnomad NFE exome AF: 0.677

Gnomad OTH exome AF: 0.638

GnomAD4 exome AF: 0.659 AC: 961123 AN: 1457638 Hom.: 323790 Cov.: 44 AF XY: 0.663 AC XY: 480822 AN XY: 725398

Gnomad4 AFR exome AF: 0.545

Gnomad4 AMR exome AF: 0.447

Gnomad4 ASJ exome AF: 0.747

Gnomad4 EAS exome AF: 0.275

Gnomad4 SAS exome AF: 0.697

Gnomad4 FIN exome AF: 0.682

Gnomad4 NFE exome AF: 0.679

Gnomad4 OTH exome AF: 0.659

GnomAD4 genome AF: 0.622 AC: 94345 AN: 151762 Hom.: 29815 Cov.: 30 AF XY: 0.623 AC XY: 46252 AN XY: 74184

Gnomad4 AFR AF: 0.549

Gnomad4 AMR AF: 0.562

Gnomad4 ASJ AF: 0.749

Gnomad4 EAS AF: 0.343

Gnomad4 SAS AF: 0.664

Gnomad4 FIN AF: 0.687

Gnomad4 NFE AF: 0.678

Gnomad4 OTH AF: 0.639

Alfa AF: 0.672 Hom.: 47318

Bravo AF: 0.602

Asia WGS AF: 0.506 AC: 1761 AN: 3478

EpiCase AF: 0.691

EpiControl AF: 0.695

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.57
DANN	Benign	0.54

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

Publications

LitVar

Other links and lift over

dbSNP: rs2484173; hg19: chr10-27687994; COSMIC: COSV71256302;