rs2505323

Positions:

• chr10-27398296-A-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM4 BA1

The NM_001034842.5(PTCHD3):​c.2302T>C​(p.Ter768Glnext*?) variant causes a stop lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.655 in 1,514,086 control chromosomes in the GnomAD database, including 331,130 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 (29896 hom., cov: 33)
  • Exomes 𝑓: 0.66 (301234 hom.)
• Consequence: PTCHD3 NM_001034842.5 stop_lost
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0920

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 Likely_benign. Variant got -6 ACMG points.

• PM4: Stoplost variant in NM_001034842.5 Downstream stopcodon found after 9 codons.
• 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.2302T>C	p.Ter768Glnext*?	stop_lost	4/4		NP_001030014.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTCHD3	ENST00000642324.1	c.2302T>C	p.Ter768Glnext*?	stop_lost	4/4			ENSP00000495205.1

Frequencies

GnomAD3 genomes AF: 0.622 AC: 94487 AN: 151946 Hom.: 29866 Cov.: 33

Gnomad AFR AF: 0.549

Gnomad AMI AF: 0.746

Gnomad AMR AF: 0.563

Gnomad ASJ AF: 0.749

Gnomad EAS AF: 0.342

Gnomad SAS AF: 0.663

Gnomad FIN AF: 0.688

Gnomad MID AF: 0.706

Gnomad NFE AF: 0.678

Gnomad OTH AF: 0.644

GnomAD3 exomes AF: 0.615 AC: 132739 AN: 215748 Hom.: 42552 AF XY: 0.629 AC XY: 73068 AN XY: 116110

Gnomad AFR exome AF: 0.545

Gnomad AMR exome AF: 0.438

Gnomad ASJ exome AF: 0.750

Gnomad EAS exome AF: 0.348

Gnomad SAS exome AF: 0.693

Gnomad FIN exome AF: 0.679

Gnomad NFE exome AF: 0.678

Gnomad OTH exome AF: 0.636

GnomAD4 exome AF: 0.658 AC: 896709 AN: 1362022 Hom.: 301234 Cov.: 22 AF XY: 0.662 AC XY: 448328 AN XY: 677708

Gnomad4 AFR exome AF: 0.545

Gnomad4 AMR exome AF: 0.455

Gnomad4 ASJ exome AF: 0.745

Gnomad4 EAS exome AF: 0.274

Gnomad4 SAS exome AF: 0.695

Gnomad4 FIN exome AF: 0.682

Gnomad4 NFE exome AF: 0.677

Gnomad4 OTH exome AF: 0.658

GnomAD4 genome AF: 0.622 AC: 94570 AN: 152064 Hom.: 29896 Cov.: 33 AF XY: 0.624 AC XY: 46377 AN XY: 74348

Gnomad4 AFR AF: 0.550

Gnomad4 AMR AF: 0.562

Gnomad4 ASJ AF: 0.749

Gnomad4 EAS AF: 0.342

Gnomad4 SAS AF: 0.664

Gnomad4 FIN AF: 0.688

Gnomad4 NFE AF: 0.678

Gnomad4 OTH AF: 0.640

Alfa AF: 0.664 Hom.: 69378

Bravo AF: 0.602

TwinsUK AF: 0.682 AC: 2528

ALSPAC AF: 0.680 AC: 2620

ESP6500AA AF: 0.535 AC: 2355

ESP6500EA AF: 0.682 AC: 5857

ExAC AF: 0.616 AC: 74600

Asia WGS AF: 0.507 AC: 1763 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.86	T
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.2
DANN	Benign	0.57
Eigen	Benign	0.065
Eigen_PC	Benign	-0.29
FATHMM_MKL	Benign	0.0015	N
Vest4		0.043
GERP RS		3.5

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: rs2505323; hg19: chr10-27687225; COSMIC: COSV71256300;