Genetic Variant PTPDC1:p.Tyr209His (chr9-94095325-T-C) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_001253829.2(PTPDC1):c.625T>C(p.Tyr209His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000691 in 1,448,134 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y209D) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

PTPDC1
NM_001253829.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.43

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.77

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPDC1	NM_001253829.2 link	c.625T>C	p.Tyr209His	missense_variant	Exon 5 of 9	ENST00000620992.5	NP_001240758.1	A2A3K4A0A087WTF0A8K0X7
PTPDC1	NM_152422.4 link	c.619T>C	p.Tyr207His	missense_variant	Exon 5 of 9		NP_689635.3	A2A3K4-2
PTPDC1	NM_177995.3 link	c.463T>C	p.Tyr155His	missense_variant	Exon 6 of 10		NP_818931.1	A2A3K4-1
PTPDC1	NM_001253830.2 link	c.463T>C	p.Tyr155His	missense_variant	Exon 6 of 10		NP_001240759.1	A2A3K4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PTPDC1	ENST00000620992.5 link	c.625T>C	p.Tyr209His	missense_variant	Exon 5 of 9	2	NM_001253829.2	ENSP00000477817.1	A0A087WTF0
PTPDC1	ENST00000288976.3 link	c.619T>C	p.Tyr207His	missense_variant	Exon 5 of 9	1		ENSP00000288976.3	A2A3K4-2
PTPDC1	ENST00000375360.7 link	c.463T>C	p.Tyr155His	missense_variant	Exon 6 of 10	1		ENSP00000364509.3	A2A3K4-1
PTPDC1	ENST00000650567.1 link	c.463T>C	p.Tyr155His	missense_variant	Exon 7 of 11			ENSP00000497158.1	A2A3K4-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.91e-7

AC:

AN:

1448134

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

720046

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32702

American (AMR)

AF:

0.00

AC:

AN:

41098

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25538

East Asian (EAS)

AF:

0.00

AC:

AN:

39632

South Asian (SAS)

AF:

0.0000121

AC:

AN:

82872

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53298

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5702

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1107348

Other (OTH)

AF:

0.00

AC:

AN:

59944

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.95

BayesDel_addAF

Pathogenic

0.22

BayesDel_noAF

Uncertain

0.080

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.36

T;T;T;.

Eigen

Uncertain

0.57

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.97

.;D;D;D

M_CAP

Benign

0.023

MetaRNN

Pathogenic

0.77

D;D;D;D

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

L;L;.;.

PhyloP100

7.4

PrimateAI

Pathogenic

0.86

PROVEAN

Uncertain

-4.4

D;.;.;D

REVEL

Uncertain

0.45

Sift

Pathogenic

0.0

D;.;.;D

Sift4G

Pathogenic

0.0

D;.;D;D

Polyphen

1.0

D;D;.;D

Vest4

0.92

MutPred

0.69

Loss of stability (P = 0.024);Loss of stability (P = 0.024);.;.;

MVP

0.41

MPC

0.68

ClinPred

0.99

GERP RS

5.7

Varity_R

0.80

gMVP

0.86

Mutation Taster

=33/67

disease causing

(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