Genetic Variant PTCHD3:p.Met521Lys (chr10-27399036-A-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000642324.1(PTCHD3):c.1562T>A(p.Met521Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 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: not found (cov: 30)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PTCHD3
ENST00000642324.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.03

Publications

33 publications found

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:

ENSG00000301548 (HGNC:):

ENSG00000301548 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.20896652).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTCHD3	NM_001034842.5 link	c.1562T>A	p.Met521Lys	missense_variant	Exon 4 of 4		NP_001030014.2	Q3KNS1A0A8Q3VUI5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTCHD3	ENST00000642324.1 link	c.1562T>A	p.Met521Lys	missense_variant	Exon 4 of 4			ENSP00000495205.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1460712

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726736

African (AFR)

AF:

0.00

AC:

AN:

33470

American (AMR)

AF:

0.00

AC:

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26126

East Asian (EAS)

AF:

0.00

AC:

AN:

39692

South Asian (SAS)

AF:

0.00

AC:

AN:

86226

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110944

Other (OTH)

AF:

0.00

AC:

AN:

60356

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

103876

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.44

BayesDel_addAF

Uncertain

0.019

BayesDel_noAF

Benign

-0.21

CADD

Benign

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.35

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.41

FATHMM_MKL

Benign

0.75

M_CAP

Benign

0.052

MetaRNN

Benign

0.21

MetaSVM

Benign

-0.39

MutationAssessor

Benign

0.0

PhyloP100

4.0

PrimateAI

Benign

0.47

PROVEAN

Benign

-1.0

REVEL

Uncertain

0.37

Sift

Uncertain

0.0070

Sift4G

Uncertain

0.0060

Polyphen

0.036

Vest4

0.38

MutPred

0.65

Gain of catalytic residue at M521 (P = 0.0014);

MVP

0.12

MPC

0.16

ClinPred

0.28

GERP RS

4.1

Varity_R

0.60

Mutation Taster

=86/14

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over