rs2505327

Positions:

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

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001034842.5(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. 14/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.62 (29857 hom., cov: 30)
  • Exomes 𝑓: 0.66 (323975 hom.)
• Consequence: PTCHD3 NM_001034842.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.03

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 -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/exons	MANE	Protein	UniProt
PTCHD3	NM_001034842.5	c.1562T>C	p.Met521Thr	missense_variant	4/4		NP_001030014.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTCHD3	ENST00000642324.1	c.1562T>C	p.Met521Thr	missense_variant	4/4			ENSP00000495205	P1

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

GnomAD3 exomes AF: 0.615 AC: 154447 AN: 251152 Hom.: 49673 AF XY: 0.631 AC XY: 85624 AN XY: 135754

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

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

Gnomad4 AFR AF: 0.549

Gnomad4 AMR AF: 0.562

Gnomad4 ASJ AF: 0.749

Gnomad4 EAS AF: 0.343

Gnomad4 SAS AF: 0.665

Gnomad4 FIN AF: 0.687

Gnomad4 NFE AF: 0.678

Gnomad4 OTH AF: 0.639

Alfa AF: 0.665 Hom.: 74104

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
MutationTaster	Benign	0.99	P
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

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: rs2505327; hg19: chr10-27687965; COSMIC: COSV71256301;