Variant rs2484180 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.05

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 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	Protein	UniProt
PTCHD3	NM_001034842.5 linkuse as main transcript	c.1219T>G	p.Cys407Gly	missense_variant	3/4		NP_001030014.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTCHD3	ENST00000642324.1 linkuse as main transcript	c.1219T>G	p.Cys407Gly	missense_variant	3/4			ENSP00000495205	P1

Frequencies

GnomAD3 genomes

AF:

0.409

AC:

62113

AN:

151780

Hom.:

12890

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.393

AC XY:

284658

AN XY:

724934

show subpopulations

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.:

AF XY:

0.410

AC XY:

30409

AN XY:

74256

show subpopulations

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

BayesDel_noAF

Benign

-0.30

CADD

Benign

DANN

Benign

0.78

DEOGEN2

Benign

0.25

T;.

Eigen

Benign

-0.16

Eigen_PC

Benign

-0.18

FATHMM_MKL

Benign

0.56

MetaRNN

Benign

0.0031

T;T

MetaSVM

Benign

-0.89

MutationAssessor

Uncertain

2.5

M;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.35

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

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over