Genetic Variant PTPDC1:p.Arg23Leu (chr9-94084598-G-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001253829.2(PTPDC1):c.68G>T(p.Arg23Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,232 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R23H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

PTPDC1
NM_001253829.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.70

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPDC1	NM_001253829.2 link	c.68G>T	p.Arg23Leu	missense_variant	Exon 1 of 9	ENST00000620992.5	NP_001240758.1	A2A3K4A0A087WTF0A8K0X7
PTPDC1	NM_152422.4 link	c.68G>T	p.Arg23Leu	missense_variant	Exon 1 of 9		NP_689635.3	A2A3K4-2
PTPDC1	NM_177995.3 link	c.83-653G>T		intron_variant	Intron 2 of 9		NP_818931.1	A2A3K4-1
PTPDC1	NM_001253830.2 link	c.83-653G>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.68G>T	p.Arg23Leu	missense_variant	Exon 1 of 9	2	NM_001253829.2	ENSP00000477817.1	A0A087WTF0
PTPDC1	ENST00000288976.3 link	c.68G>T	p.Arg23Leu	missense_variant	Exon 1 of 9	1		ENSP00000288976.3	A2A3K4-2
PTPDC1	ENST00000375360.7 link	c.83-653G>T		intron_variant	Intron 2 of 9	1		ENSP00000364509.3	A2A3K4-1
PTPDC1	ENST00000650567.1 link	c.83-653G>T		intron_variant	Intron 3 of 10			ENSP00000497158.1	A2A3K4-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000121

AC:

AN:

248340

AF XY:

0.00000742

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000580

Gnomad ASJ exome

AF:

0.00

Gnomad EAS 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:

0.00000274

AC:

AN:

1461232

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726938

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33458

American (AMR)

AF:

0.0000448

AC:

AN:

44676

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26094

East Asian (EAS)

AF:

0.00

AC:

AN:

39660

South Asian (SAS)

AF:

0.0000232

AC:

AN:

86180

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53174

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5720

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111892

Other (OTH)

AF:

0.00

AC:

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.44

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.027

T;.

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.83

T;T

M_CAP

Benign

0.069

MetaRNN

Uncertain

0.73

D;D

MetaSVM

Benign

-1.1

PhyloP100

5.7

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-1.5

.;N

REVEL

Benign

0.17

Sift

Uncertain

0.0010

.;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

.;D

Vest4

0.78

MutPred

0.39

Loss of methylation at R23 (P = 0.0201);Loss of methylation at R23 (P = 0.0201);

MVP

0.44

MPC

0.65

ClinPred

0.97

GERP RS

4.9

PromoterAI

0.013

Neutral

(source)

gMVP

0.48

Mutation Taster

=73/27

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

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chr9-94084598-G-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over