9-94088147-A-G

Variant names:

Variant summary

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

The NM_001253829.2(PTPDC1):c.500A>G(p.His167Arg) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,612,430 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

PTPDC1
NM_001253829.2 missense, splice_region

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.83

Publications

1 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:

Genome browser will be placed here

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=0.1314623).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPDC1	NM_001253829.2 link	c.500A>G	p.His167Arg	missense_variant, splice_region_variant	Exon 4 of 9	ENST00000620992.5	NP_001240758.1	A2A3K4A0A087WTF0A8K0X7
PTPDC1	NM_152422.4 link	c.494A>G	p.His165Arg	missense_variant, splice_region_variant	Exon 4 of 9		NP_689635.3	A2A3K4-2
PTPDC1	NM_177995.3 link	c.338A>G	p.His113Arg	missense_variant, splice_region_variant	Exon 5 of 10		NP_818931.1	A2A3K4-1
PTPDC1	NM_001253830.2 link	c.338A>G	p.His113Arg	missense_variant, splice_region_variant	Exon 5 of 10		NP_001240759.1	A2A3K4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PTPDC1	ENST00000620992.5 link	c.500A>G	p.His167Arg	missense_variant, splice_region_variant	Exon 4 of 9	2	NM_001253829.2	ENSP00000477817.1	A0A087WTF0
PTPDC1	ENST00000288976.3 link	c.494A>G	p.His165Arg	missense_variant, splice_region_variant	Exon 4 of 9	1		ENSP00000288976.3	A2A3K4-2
PTPDC1	ENST00000375360.7 link	c.338A>G	p.His113Arg	missense_variant, splice_region_variant	Exon 5 of 10	1		ENSP00000364509.3	A2A3K4-1
PTPDC1	ENST00000650567.1 link	c.338A>G	p.His113Arg	missense_variant, splice_region_variant	Exon 6 of 11			ENSP00000497158.1	A2A3K4-1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152096

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1460334

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726354

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33416

American (AMR)

AF:

0.00

AC:

AN:

44502

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26068

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.0000350

AC:

AN:

85740

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53406

Middle Eastern (MID)

AF:

0.000180

AC:

AN:

5548

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111634

Other (OTH)

AF:

0.0000166

AC:

AN:

60324

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152096

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74304

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

41392

American (AMR)

AF:

0.00

AC:

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000192

AC:

AN:

5202

South Asian (SAS)

AF:

0.000208

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68010

Other (OTH)

AF:

0.00

AC:

AN:

2092

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.029673), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.400

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000151

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 21, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.494A>G (p.H165R) alteration is located in exon 4 (coding exon 4) of the PTPDC1 gene. This alteration results from a A to G substitution at nucleotide position 494, causing the histidine (H) at amino acid position 165 to be replaced by an arginine (R). 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

Benign

0.073

BayesDel_addAF

Benign

-0.073

BayesDel_noAF

Benign

-0.34

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.017

T;T;T;.

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.041

FATHMM_MKL

Benign

0.67

LIST_S2

Uncertain

0.93

.;D;D;D

M_CAP

Benign

0.014

MetaRNN

Benign

0.13

T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.99

L;L;.;.

PhyloP100

1.8

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.2

N;.;.;N

REVEL

Benign

0.10

Sift

Benign

0.35

T;.;.;T

Sift4G

Benign

0.34

T;.;T;T

Polyphen

0.045

B;B;.;B

Vest4

0.24

MutPred

0.54

Loss of sheet (P = 0.007);Loss of sheet (P = 0.007);.;.;

MVP

0.71

MPC

0.16

ClinPred

0.23

GERP RS

3.6

Varity_R

0.053

gMVP

0.83

Mutation Taster

=93/7

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

9-94088147-A-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over