Variant 10-27399226-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PP3_Strong

The NM_001034842.5(PTCHD3):c.1372G>T(p.Asp458Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 26)

Exomes 𝑓: 0.000021 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PTCHD3
NM_001034842.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.01

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 Uncertain_significance. Variant got 4 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.957

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTCHD3	NM_001034842.5 linkuse as main transcript	c.1372G>T	p.Asp458Tyr	missense_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTCHD3	ENST00000642324.1 linkuse as main transcript	c.1372G>T	p.Asp458Tyr	missense_variant	4/4			P1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

143426

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000183

AC:

AN:

218042

Hom.:

AF XY:

0.0000168

AC XY:

AN XY:

119146

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000979

Gnomad OTH exome

AF:

0.000554

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000215

AC:

AN:

1397668

Hom.:

Cov.:

AF XY:

0.0000187

AC XY:

AN XY:

696138

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000122

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000224

Gnomad4 OTH exome

AF:

0.0000171

GnomAD4 genome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

143500

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

69166

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000509

Hom.:

ExAC

AF:

0.0000165

AC:

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

Jan 24, 2024

The c.1372G>T (p.D458Y) 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 1372, causing the aspartic acid (D) at amino acid position 458 to be replaced by a tyrosine (Y). 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

Uncertain

0.37

BayesDel_addAF

Uncertain

0.16

BayesDel_noAF

Uncertain

0.070

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.37

T;.

Eigen

Benign

0.16

Eigen_PC

Benign

0.040

FATHMM_MKL

Uncertain

0.87

M_CAP

Uncertain

0.23

MetaRNN

Pathogenic

0.96

D;D

MetaSVM

Uncertain

0.73

MutationAssessor

Uncertain

2.7

M;.

MutationTaster

Benign

0.99

PrimateAI

Benign

0.46

PROVEAN

Pathogenic

-7.4

D;.

REVEL

Pathogenic

0.70

Sift

Uncertain

0.0020

D;.

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;.

Vest4

0.61

MutPred

0.86

Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);

MVP

0.54

MPC

0.56

ClinPred

0.77

GERP RS

2.8

Varity_R

0.91

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