9-94097368-G-A

Position:

chr9-94097368-G-A

Variant summary

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

The NM_001253829.2(PTPDC1):c.802G>A(p.Asp268Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000198 in 1,613,498 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 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

PTPDC1
NM_001253829.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.52

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 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=0.1278196).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPDC1	NM_001253829.2 link	c.802G>A	p.Asp268Asn	missense_variant	6/9	ENST00000620992.5	NP_001240758.1	A2A3K4A0A087WTF0A8K0X7
PTPDC1	NM_152422.4 link	c.796G>A	p.Asp266Asn	missense_variant	6/9		NP_689635.3	A2A3K4-2
PTPDC1	NM_177995.3 link	c.640G>A	p.Asp214Asn	missense_variant	7/10		NP_818931.1	A2A3K4-1
PTPDC1	NM_001253830.2 link	c.640G>A	p.Asp214Asn	missense_variant	7/10		NP_001240759.1	A2A3K4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PTPDC1	ENST00000620992.5 link	c.802G>A	p.Asp268Asn	missense_variant	6/9	2	NM_001253829.2	ENSP00000477817.1	A0A087WTF0
PTPDC1	ENST00000288976.3 link	c.796G>A	p.Asp266Asn	missense_variant	6/9	1		ENSP00000288976.3	A2A3K4-2
PTPDC1	ENST00000375360.7 link	c.640G>A	p.Asp214Asn	missense_variant	7/10	1		ENSP00000364509.3	A2A3K4-1
PTPDC1	ENST00000650567.1 link	c.640G>A	p.Asp214Asn	missense_variant	8/11			ENSP00000497158.1	A2A3K4-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152164

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:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000717

AC:

AN:

251056

Hom.:

AF XY:

0.0000663

AC XY:

AN XY:

135654

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000557

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000212

AC:

AN:

1461216

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

726782

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000325

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152282

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ExAC

AF:

0.000107

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 05, 2024

The c.796G>A (p.D266N) alteration is located in exon 6 (coding exon 6) of the PTPDC1 gene. This alteration results from a G to A substitution at nucleotide position 796, causing the aspartic acid (D) at amino acid position 266 to be replaced by an asparagine (N). 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

0.32

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.31

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.18

T;T;T;.

Eigen

Uncertain

0.20

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.94

.;D;D;D

M_CAP

Benign

0.045

MetaRNN

Benign

0.13

T;T;T;T

MetaSVM

Benign

-0.31

MutationAssessor

Benign

0.18

N;N;.;.

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-0.96

N;.;.;N

REVEL

Uncertain

0.38

Sift

Benign

0.26

T;.;.;T

Sift4G

Benign

0.65

T;.;T;T

Polyphen

0.79

P;P;.;P

Vest4

0.27

MutPred

0.54

Gain of MoRF binding (P = 0.0418);Gain of MoRF binding (P = 0.0418);.;.;

MVP

0.78

MPC

0.21

ClinPred

0.15

GERP RS

5.5

Varity_R

0.21

gMVP

0.69

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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