Variant 9-94097483-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001253829.2(PTPDC1):c.917C>T(p.Ser306Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,842 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S306C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

PTPDC1
NM_001253829.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.41

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PTPDC1	NM_001253829.2 linkuse as main transcript	c.917C>T	p.Ser306Phe	missense_variant	6/9	ENST00000620992.5
PTPDC1	NM_152422.4 linkuse as main transcript	c.911C>T	p.Ser304Phe	missense_variant	6/9
PTPDC1	NM_177995.3 linkuse as main transcript	c.755C>T	p.Ser252Phe	missense_variant	7/10
PTPDC1	NM_001253830.2 linkuse as main transcript	c.755C>T	p.Ser252Phe	missense_variant	7/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPDC1	ENST00000620992.5 linkuse as main transcript	c.917C>T	p.Ser306Phe	missense_variant	6/9	2	NM_001253829.2
PTPDC1	ENST00000288976.3 linkuse as main transcript	c.911C>T	p.Ser304Phe	missense_variant	6/9	1			A2A3K4-2
PTPDC1	ENST00000375360.7 linkuse as main transcript	c.755C>T	p.Ser252Phe	missense_variant	7/10	1		P1	A2A3K4-1
PTPDC1	ENST00000650567.1 linkuse as main transcript	c.755C>T	p.Ser252Phe	missense_variant	8/11			P1	A2A3K4-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000795

AC:

AN:

251466

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135914

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461842

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727218

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

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

Mar 23, 2023

The c.911C>T (p.S304F) alteration is located in exon 6 (coding exon 6) of the PTPDC1 gene. This alteration results from a C to T substitution at nucleotide position 911, causing the serine (S) at amino acid position 304 to be replaced by a phenylalanine (F). 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

0.48

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.22

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.27

T;T;T;.

Eigen

Pathogenic

0.77

Eigen_PC

Pathogenic

0.76

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.95

.;D;D;D

M_CAP

Benign

0.018

MetaRNN

Uncertain

0.57

D;D;D;D

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

L;L;.;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.59

PROVEAN

Uncertain

-3.2

D;.;.;D

REVEL

Benign

0.21

Sift

Benign

0.030

D;.;.;D

Sift4G

Uncertain

0.031

D;.;D;D

Polyphen

0.99

D;D;.;D

Vest4

0.55

MutPred

0.49

Gain of ubiquitination at K257 (P = 0.0938);Gain of ubiquitination at K257 (P = 0.0938);.;.;

MVP

0.57

MPC

0.54

ClinPred

0.92

GERP RS

5.5

Varity_R

0.34

gMVP

0.46

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

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