rs2484180

chr10-27403350-A-Cchr10-27403350-A-Gchr10-27403350-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.1219T>G(p.Cys407Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.396 in 1,608,940 control chromosomes in the GnomAD database, including 128,307 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 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 0.41 (12913 hom., cov: 31)
  • Exomes 𝑓: 0.39 (115394 hom.)
• Consequence: PTCHD3 NM_001034842.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.05

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=0.003067553).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.51 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTCHD3	NM_001034842.5	c.1219T>G	p.Cys407Gly	missense_variant	3/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTCHD3	ENST00000642324.1	c.1219T>G	p.Cys407Gly	missense_variant	3/4			P1

Frequencies

GnomAD3 genomes AF: 0.409 AC: 62113 AN: 151780 Hom.: 12890 Cov.: 31

Gnomad AFR AF: 0.438

Gnomad AMI AF: 0.439

Gnomad AMR AF: 0.430

Gnomad ASJ AF: 0.382

Gnomad EAS AF: 0.527

Gnomad SAS AF: 0.375

Gnomad FIN AF: 0.341

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.392

Gnomad OTH AF: 0.424

GnomAD3 exomes AF: 0.397 AC: 98961 AN: 249072 Hom.: 20290 AF XY: 0.395 AC XY: 53178 AN XY: 134732

Gnomad AFR exome AF: 0.431

Gnomad AMR exome AF: 0.396

Gnomad ASJ exome AF: 0.373

Gnomad EAS exome AF: 0.526

Gnomad SAS exome AF: 0.381

Gnomad FIN exome AF: 0.327

Gnomad NFE exome AF: 0.392

Gnomad OTH exome AF: 0.385

GnomAD4 exome AF: 0.394 AC: 574213 AN: 1457042 Hom.: 115394 Cov.: 36 AF XY: 0.393 AC XY: 284658 AN XY: 724934

Gnomad4 AFR exome AF: 0.431

Gnomad4 AMR exome AF: 0.399

Gnomad4 ASJ exome AF: 0.369

Gnomad4 EAS exome AF: 0.478

Gnomad4 SAS exome AF: 0.377

Gnomad4 FIN exome AF: 0.339

Gnomad4 NFE exome AF: 0.394

Gnomad4 OTH exome AF: 0.401

GnomAD4 genome AF: 0.409 AC: 62179 AN: 151898 Hom.: 12913 Cov.: 31 AF XY: 0.410 AC XY: 30409 AN XY: 74256

Gnomad4 AFR AF: 0.438

Gnomad4 AMR AF: 0.429

Gnomad4 ASJ AF: 0.382

Gnomad4 EAS AF: 0.527

Gnomad4 SAS AF: 0.374

Gnomad4 FIN AF: 0.341

Gnomad4 NFE AF: 0.392

Gnomad4 OTH AF: 0.432

Alfa AF: 0.403 Hom.: 27715

Bravo AF: 0.431

TwinsUK AF: 0.393 AC: 1458

ALSPAC AF: 0.391 AC: 1507

ESP6500AA AF: 0.458 AC: 2020

ESP6500EA AF: 0.395 AC: 3397

ExAC AF: 0.399 AC: 48393

EpiCase AF: 0.400

EpiControl AF: 0.403

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.30
Cadd	Benign	19
Dann	Benign	0.78
DEOGEN2	Benign	0.25	T;.
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.18
FATHMM_MKL	Benign	0.56	D
MetaRNN	Benign	0.0031	T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Uncertain	2.5	M;.
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.35	T
PROVEAN	Uncertain	-4.2	D;.
REVEL	Uncertain	0.35
Sift	Benign	0.26	T;.
Sift4G	Uncertain	0.035	D;D
Polyphen		0.26	B;.
Vest4		0.32
MPC		0.30
ClinPred		0.053	T
GERP RS		2.9
Varity_R		0.50

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: rs2484180; hg19: chr10-27692279; COSMIC: COSV71256853;