Variant chr9-94095355-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001253829.2(PTPDC1):c.655G>A(p.Ala219Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000806 in 1,612,130 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00049 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000038 ( 0 hom. )

Consequence

PTPDC1
NM_001253829.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.43

Variant links:

Genes affected

PTPDC1 (HGNC:30184): (protein tyrosine phosphatase domain containing 1) The protein encoded by this gene contains a characteristic motif of protein tyrosine phosphatases (PTPs). PTPs regulate activities of phosphoproteins through dephosphorylation. They are signaling molecules involved in the regulation of a wide variety of biological processes. The specific function of this protein has not yet been determined. Alternatively spliced transcript variants encoding distinct isoforms have been identified. [provided by RefSeq, Jul 2008]

PTPDC1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07561377).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PTPDC1	NM_001253829.2 linkuse as main transcript	c.655G>A	p.Ala219Thr	missense_variant	5/9	ENST00000620992.5
PTPDC1	NM_152422.4 linkuse as main transcript	c.649G>A	p.Ala217Thr	missense_variant	5/9
PTPDC1	NM_177995.3 linkuse as main transcript	c.493G>A	p.Ala165Thr	missense_variant	6/10
PTPDC1	NM_001253830.2 linkuse as main transcript	c.493G>A	p.Ala165Thr	missense_variant	6/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPDC1	ENST00000620992.5 linkuse as main transcript	c.655G>A	p.Ala219Thr	missense_variant	5/9	2	NM_001253829.2
PTPDC1	ENST00000288976.3 linkuse as main transcript	c.649G>A	p.Ala217Thr	missense_variant	5/9	1			A2A3K4-2
PTPDC1	ENST00000375360.7 linkuse as main transcript	c.493G>A	p.Ala165Thr	missense_variant	6/10	1		P1	A2A3K4-1
PTPDC1	ENST00000650567.1 linkuse as main transcript	c.493G>A	p.Ala165Thr	missense_variant	7/11			P1	A2A3K4-1

Frequencies

GnomAD3 genomes

AF:

0.000493

AC:

AN:

152048

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00167

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

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:

0.0000957

AC:

AN:

250682

Hom.:

AF XY:

0.0000664

AC XY:

AN XY:

135470

show subpopulations

Gnomad AFR exome

AF:

0.00135

Gnomad AMR exome

AF:

0.0000291

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:

0.00000881

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000377

AC:

AN:

1460082

Hom.:

Cov.:

AF XY:

0.0000344

AC XY:

AN XY:

726404

show subpopulations

Gnomad4 AFR exome

AF:

0.00129

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000182

GnomAD4 genome

AF:

0.000493

AC:

AN:

152048

Hom.:

Cov.:

AF XY:

0.000364

AC XY:

AN XY:

74260

show subpopulations

Gnomad4 AFR

AF:

0.00167

Gnomad4 AMR

AF:

0.000393

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:

0.0000969

Hom.:

Bravo

AF:

0.000514

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000132

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

Dec 07, 2021

The c.649G>A (p.A217T) alteration is located in exon 5 (coding exon 5) of the PTPDC1 gene. This alteration results from a G to A substitution at nucleotide position 649, causing the alanine (A) at amino acid position 217 to be replaced by a threonine (T). 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

0.52

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Uncertain

0.020

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.28

T;T;T;.

Eigen

Uncertain

0.50

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.95

.;D;D;D

M_CAP

Benign

0.018

MetaRNN

Benign

0.076

T;T;T;T

MetaSVM

Benign

-1.2

MutationAssessor

Benign

1.4

L;L;.;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-2.1

N;.;.;N

REVEL

Benign

0.25

Sift

Benign

0.057

T;.;.;T

Sift4G

Uncertain

0.060

T;.;T;T

Polyphen

0.90

P;P;.;P

Vest4

0.77

MVP

0.58

MPC

0.38

ClinPred

0.14

GERP RS

5.7

Varity_R

0.18

gMVP

0.72

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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