9-94084751-C-T

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.221C>T(p.Thr74Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000028 in 1,427,480 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

PTPDC1
NM_001253829.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.77

Publications

2 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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15288258).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPDC1	NM_001253829.2 link	c.221C>T	p.Thr74Ile	missense_variant	Exon 1 of 9	ENST00000620992.5	NP_001240758.1	A2A3K4A0A087WTF0A8K0X7
PTPDC1	NM_152422.4 link	c.221C>T	p.Thr74Ile	missense_variant	Exon 1 of 9		NP_689635.3	A2A3K4-2
PTPDC1	NM_177995.3 link	c.83-500C>T		intron_variant	Intron 2 of 9		NP_818931.1	A2A3K4-1
PTPDC1	NM_001253830.2 link	c.83-500C>T		intron_variant	Intron 2 of 9		NP_001240759.1	A2A3K4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PTPDC1	ENST00000620992.5 link	c.221C>T	p.Thr74Ile	missense_variant	Exon 1 of 9	2	NM_001253829.2	ENSP00000477817.1	A0A087WTF0
PTPDC1	ENST00000288976.3 link	c.221C>T	p.Thr74Ile	missense_variant	Exon 1 of 9	1		ENSP00000288976.3	A2A3K4-2
PTPDC1	ENST00000375360.7 link	c.83-500C>T		intron_variant	Intron 2 of 9	1		ENSP00000364509.3	A2A3K4-1
PTPDC1	ENST00000650567.1 link	c.83-500C>T		intron_variant	Intron 3 of 10			ENSP00000497158.1	A2A3K4-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000280

AC:

AN:

1427480

Hom.:

Cov.:

AF XY:

0.00000424

AC XY:

AN XY:

708030

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31750

American (AMR)

AF:

0.00

AC:

AN:

36466

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23976

East Asian (EAS)

AF:

0.00

AC:

AN:

39286

South Asian (SAS)

AF:

0.00

AC:

AN:

80906

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52630

Middle Eastern (MID)

AF:

0.000179

AC:

AN:

5590

European-Non Finnish (NFE)

AF:

0.00000273

AC:

AN:

1098130

Other (OTH)

AF:

0.00

AC:

AN:

58746

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Sep 26, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.221C>T (p.T74I) alteration is located in exon 1 (coding exon 1) of the PTPDC1 gene. This alteration results from a C to T substitution at nucleotide position 221, causing the threonine (T) at amino acid position 74 to be replaced by an isoleucine (I). 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

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.70

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0065

T;.

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.092

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.67

T;T

M_CAP

Benign

0.0096

MetaRNN

Benign

0.15

T;T

MetaSVM

Benign

-1.0

PhyloP100

2.8

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.25

.;N

REVEL

Benign

0.042

Sift

Uncertain

0.0020

.;D

Sift4G

Benign

0.11

T;T

Polyphen

0.091

.;B

Vest4

0.27

MutPred

0.16

Gain of catalytic residue at P76 (P = 0.0309);Gain of catalytic residue at P76 (P = 0.0309);

MVP

0.35

MPC

0.15

ClinPred

0.98

GERP RS

4.8

PromoterAI

0.028

Neutral

(source)

gMVP

0.56

Mutation Taster

=94/6

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.13

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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9-94084751-C-T

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