Variant 10-27398508-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PP3_ModerateBS2

The NM_001034842.5(PTCHD3):c.2090G>T(p.Trp697Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000311 in 1,609,758 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00034 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00031 ( 2 hom. )

Consequence

PTCHD3
NM_001034842.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.58

Variant links:

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]

PTCHD3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.915

BS2

High Homozygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTCHD3	NM_001034842.5 linkuse as main transcript	c.2090G>T	p.Trp697Leu	missense_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTCHD3	ENST00000642324.1 linkuse as main transcript	c.2090G>T	p.Trp697Leu	missense_variant	4/4			P1

Frequencies

GnomAD3 genomes

AF:

0.000342

AC:

AN:

152078

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000966

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000590

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000529

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000326

AC:

AN:

248158

Hom.:

AF XY:

0.000402

AC XY:

AN XY:

134204

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000441

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000101

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000541

Gnomad OTH exome

AF:

0.000331

GnomAD4 exome

AF:

0.000309

AC:

450

AN:

1457562

Hom.:

Cov.:

AF XY:

0.000346

AC XY:

251

AN XY:

725084

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000453

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000469

Gnomad4 FIN exome

AF:

0.0000750

Gnomad4 NFE exome

AF:

0.000339

Gnomad4 OTH exome

AF:

0.000482

GnomAD4 genome

AF:

0.000335

AC:

AN:

152196

Hom.:

Cov.:

AF XY:

0.000403

AC XY:

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.0000963

Gnomad4 AMR

AF:

0.000589

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.000529

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000579

Hom.:

Bravo

AF:

0.000336

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000583

AC:

ExAC

AF:

0.000429

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000709

EpiControl

AF:

0.00125

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 16, 2021

The c.2090G>T (p.W697L) alteration is located in exon 4 (coding exon 4) of the PTCHD3 gene. This alteration results from a G to T substitution at nucleotide position 2090, causing the tryptophan (W) at amino acid position 697 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.79

BayesDel_addAF

Benign

-0.094

BayesDel_noAF

Uncertain

-0.020

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.59

Eigen

Uncertain

0.58

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Uncertain

0.96

M_CAP

Uncertain

0.16

MetaRNN

Pathogenic

0.92

MetaSVM

Pathogenic

0.86

MutationAssessor

Uncertain

2.8

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.51

PROVEAN

Pathogenic

-11

REVEL

Uncertain

0.61

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.68

MVP

0.51

MPC

0.68

ClinPred

0.95

GERP RS

4.2

Varity_R

0.93

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over