chr10-27403350-A-C

Variant names:

• chr10-27403350-A-C
• rs2484180
• ENST00000642324.1:c.1219T>G

Variant summary

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

The ENST00000642324.1(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. 12/20 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 0.41 (12913 hom., cov: 31)
  • Exomes 𝑓: 0.39 (115394 hom.)
• Consequence: PTCHD3 ENST00000642324.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.05
• Publications: 28 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=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 rank	MANE	Protein	UniProt
PTCHD3	NM_001034842.5	c.1219T>G	p.Cys407Gly	missense_variant	Exon 3 of 4		NP_001030014.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTCHD3	ENST00000642324.1	c.1219T>G	p.Cys407Gly	missense_variant	Exon 3 of 4			ENSP00000495205.1

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

GnomAD2 exomes AF: 0.397 AC: 98961 AN: 249072 AF XY: 0.395

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 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

African (AFR) AF: 0.431 AC: 14398 AN: 33408

American (AMR) AF: 0.399 AC: 17792 AN: 44570

Ashkenazi Jewish (ASJ) AF: 0.369 AC: 9637 AN: 26110

East Asian (EAS) AF: 0.478 AC: 18924 AN: 39622

South Asian (SAS) AF: 0.377 AC: 32375 AN: 85968

European-Finnish (FIN) AF: 0.339 AC: 17848 AN: 52594

Middle Eastern (MID) AF: 0.393 AC: 2265 AN: 5764

European-Non Finnish (NFE) AF: 0.394 AC: 436809 AN: 1108756

Other (OTH) AF: 0.401 AC: 24165 AN: 60250

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

African (AFR) AF: 0.438 AC: 18116 AN: 41386

American (AMR) AF: 0.429 AC: 6554 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.382 AC: 1324 AN: 3470

East Asian (EAS) AF: 0.527 AC: 2718 AN: 5160

South Asian (SAS) AF: 0.374 AC: 1801 AN: 4814

European-Finnish (FIN) AF: 0.341 AC: 3606 AN: 10568

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.392 AC: 26639 AN: 67922

Other (OTH) AF: 0.432 AC: 909 AN: 2106

Alfa AF: 0.411 Hom.: 40361

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;.
PhyloP100		2.0
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
Mutation Taster		=99/1	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: rs2484180; hg19: chr10-27692279; COSMIC: COSV71256853;