rs2505327

Variant names:

• chr10-27399036-A-G
• rs2505327
• ENST00000642324.1:c.1562T>C

Your query was ambiguous. Multiple possible variants found:

• chr10-27399036-A-G
• chr10-27399036-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000642324.1(PTCHD3):​c.1562T>C​(p.Met521Thr) variant causes a missense change. The variant allele was found at a frequency of 0.656 in 1,611,132 control chromosomes in the GnomAD database, including 353,832 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict 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 (29857 hom., cov: 30)
  • Exomes 𝑓: 0.66 (323975 hom.)
• Consequence: PTCHD3 ENST00000642324.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.03
• Publications: 33 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.2129038E-6).
• 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.1562T>C	p.Met521Thr	missense_variant	Exon 4 of 4		NP_001030014.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTCHD3	ENST00000642324.1	c.1562T>C	p.Met521Thr	missense_variant	Exon 4 of 4			ENSP00000495205.1

Frequencies

GnomAD3 genomes AF: 0.622 AC: 94369 AN: 151808 Hom.: 29827 Cov.: 30

Gnomad AFR AF: 0.549

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

GnomAD2 exomes AF: 0.615 AC: 154447 AN: 251152 AF XY: 0.631

Gnomad AFR exome AF: 0.545

Gnomad AMR exome AF: 0.429

Gnomad ASJ exome AF: 0.749

Gnomad EAS exome AF: 0.350

Gnomad FIN exome AF: 0.679

Gnomad NFE exome AF: 0.677

Gnomad OTH exome AF: 0.638

GnomAD4 exome AF: 0.659 AC: 962128 AN: 1459206 Hom.: 323975 Cov.: 42 AF XY: 0.663 AC XY: 481227 AN XY: 726034

African (AFR) AF: 0.545 AC: 18219 AN: 33438

American (AMR) AF: 0.447 AC: 19999 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.747 AC: 19508 AN: 26114

East Asian (EAS) AF: 0.275 AC: 10902 AN: 39678

South Asian (SAS) AF: 0.697 AC: 60036 AN: 86192

European-Finnish (FIN) AF: 0.682 AC: 36441 AN: 53412

Middle Eastern (MID) AF: 0.739 AC: 4257 AN: 5762

European-Non Finnish (NFE) AF: 0.679 AC: 753047 AN: 1109598

Other (OTH) AF: 0.659 AC: 39719 AN: 60298

GnomAD4 genome AF: 0.622 AC: 94452 AN: 151926 Hom.: 29857 Cov.: 30 AF XY: 0.624 AC XY: 46316 AN XY: 74280

African (AFR) AF: 0.549 AC: 22763 AN: 41444

American (AMR) AF: 0.562 AC: 8567 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.749 AC: 2597 AN: 3466

East Asian (EAS) AF: 0.343 AC: 1774 AN: 5174

South Asian (SAS) AF: 0.665 AC: 3198 AN: 4812

European-Finnish (FIN) AF: 0.687 AC: 7247 AN: 10542

Middle Eastern (MID) AF: 0.705 AC: 206 AN: 292

European-Non Finnish (NFE) AF: 0.678 AC: 46071 AN: 67928

Other (OTH) AF: 0.639 AC: 1349 AN: 2110

Alfa AF: 0.656 Hom.: 103876

Bravo AF: 0.602

TwinsUK AF: 0.682 AC: 2528

ALSPAC AF: 0.675 AC: 2603

ESP6500AA AF: 0.535 AC: 2356

ESP6500EA AF: 0.682 AC: 5860

ExAC AF: 0.619 AC: 75096

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
AlphaMissense	Benign	0.055
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	8.4
DANN	Benign	0.30
DEOGEN2	Benign	0.044	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.031	N
MetaRNN	Benign	0.0000022	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-2.6	N
PhyloP100		4.0
PrimateAI	Benign	0.45	T
PROVEAN	Benign	3.1	N
REVEL	Benign	0.18
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.061
MPC		0.11
ClinPred		0.0015	T
GERP RS		4.1
Varity_R		0.046
Mutation Taster		=88/12	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: rs2505327; hg19: chr10-27687965; COSMIC: COSV71256301;