Variant 10-27398499-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001034842.5(PTCHD3):c.2099C>T(p.Ala700Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000118 in 1,608,512 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00020 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

PTCHD3
NM_001034842.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.854

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.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.043622434).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTCHD3	NM_001034842.5 linkuse as main transcript	c.2099C>T	p.Ala700Val	missense_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTCHD3	ENST00000642324.1 linkuse as main transcript	c.2099C>T	p.Ala700Val	missense_variant	4/4			P1

Frequencies

GnomAD3 genomes

AF:

0.000197

AC:

AN:

152012

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.000109

AC:

AN:

248270

Hom.:

AF XY:

0.0000968

AC XY:

AN XY:

134240

show subpopulations

Gnomad AFR exome

AF:

0.000250

Gnomad AMR exome

AF:

0.000147

Gnomad ASJ exome

AF:

0.000202

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000133

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.000110

AC:

160

AN:

1456382

Hom.:

Cov.:

AF XY:

0.000109

AC XY:

AN XY:

724530

show subpopulations

Gnomad4 AFR exome

AF:

0.000332

Gnomad4 AMR exome

AF:

0.000136

Gnomad4 ASJ exome

AF:

0.0000769

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000235

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000115

Gnomad4 OTH exome

AF:

0.000150

GnomAD4 genome

AF:

0.000197

AC:

AN:

152130

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.000169

Gnomad4 AMR

AF:

0.000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.0000388

Hom.:

Bravo

AF:

0.000185

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000659

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.00

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

Apr 13, 2022

The c.2099C>T (p.A700V) alteration is located in exon 4 (coding exon 4) of the PTCHD3 gene. This alteration results from a C to T substitution at nucleotide position 2099, causing the alanine (A) at amino acid position 700 to be replaced by a valine (V). 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

Benign

0.13

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.38

CADD

Benign

3.6

DANN

Benign

0.57

DEOGEN2

Benign

0.13

Eigen

Benign

-0.97

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.037

M_CAP

Benign

0.051

MetaRNN

Benign

0.044

MetaSVM

Benign

-0.79

MutationAssessor

Benign

0.60

MutationTaster

Benign

1.0

PrimateAI

Benign

0.28

PROVEAN

Benign

-1.2

REVEL

Benign

0.12

Sift

Benign

0.36

Sift4G

Benign

0.37

Polyphen

0.082

Vest4

0.095

MVP

0.12

MPC

0.10

ClinPred

0.010

GERP RS

0.60

Varity_R

0.066

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