rs2505323

Variant names:

• chr10-27398296-A-G
• rs2505323
• ENST00000642324.1:c.2302T>C

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 2P and 8B. PM4 BA1

The ENST00000642324.1(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 ENST00000642324.1 stop_lost
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0920
• Publications: 32 publications found

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]

ENSG00000301548 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• PM4: Stoplost variant in ENST00000642324.1 Downstream stopcodon found after 372 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 rank	MANE	Protein	UniProt
PTCHD3	NM_001034842.5	c.2302T>C	p.Ter768Glnext*?	stop_lost	Exon 4 of 4		NP_001030014.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTCHD3	ENST00000642324.1	c.2302T>C	p.Ter768Glnext*?	stop_lost	Exon 4 of 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

GnomAD2 exomes AF: 0.615 AC: 132739 AN: 215748 AF XY: 0.629

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 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

African (AFR) AF: 0.545 AC: 16637 AN: 30522

American (AMR) AF: 0.455 AC: 16550 AN: 36364

Ashkenazi Jewish (ASJ) AF: 0.745 AC: 17422 AN: 23372

East Asian (EAS) AF: 0.274 AC: 10716 AN: 39124

South Asian (SAS) AF: 0.695 AC: 53250 AN: 76566

European-Finnish (FIN) AF: 0.682 AC: 35458 AN: 51966

Middle Eastern (MID) AF: 0.739 AC: 4018 AN: 5438

European-Non Finnish (NFE) AF: 0.677 AC: 705378 AN: 1042024

Other (OTH) AF: 0.658 AC: 37280 AN: 56646

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

African (AFR) AF: 0.550 AC: 22809 AN: 41490

American (AMR) AF: 0.562 AC: 8585 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.749 AC: 2600 AN: 3472

East Asian (EAS) AF: 0.342 AC: 1774 AN: 5180

South Asian (SAS) AF: 0.664 AC: 3198 AN: 4818

European-Finnish (FIN) AF: 0.688 AC: 7282 AN: 10582

Middle Eastern (MID) AF: 0.707 AC: 208 AN: 294

European-Non Finnish (NFE) AF: 0.678 AC: 46083 AN: 67942

Other (OTH) AF: 0.640 AC: 1351 AN: 2110

Alfa AF: 0.655 Hom.: 99201

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
PhyloP100		0.092
Vest4		0.043
GERP RS		3.5
Mutation Taster		=159/41	polymorphism (auto)

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