9-94085353-C-T

Variant names:

• chr9-94085353-C-T
• rs567274018
• NM_001253829.2:c.347C>T

Variant summary

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

The NM_001253829.2(PTPDC1):​c.347C>T​(p.Ala116Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000867 in 1,614,052 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000085 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000087 (0 hom.)
• Consequence: PTPDC1 NM_001253829.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.66

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]

ACMG classification

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 rank	MANE	Protein	UniProt
PTPDC1	NM_001253829.2	c.347C>T	p.Ala116Val	missense_variant	Exon 2 of 9	ENST00000620992.5	NP_001240758.1
PTPDC1	NM_152422.4	c.341C>T	p.Ala114Val	missense_variant	Exon 2 of 9		NP_689635.3
PTPDC1	NM_177995.3	c.185C>T	p.Ala62Val	missense_variant	Exon 3 of 10		NP_818931.1
PTPDC1	NM_001253830.2	c.185C>T	p.Ala62Val	missense_variant	Exon 3 of 10		NP_001240759.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPDC1	ENST00000620992.5	c.347C>T	p.Ala116Val	missense_variant	Exon 2 of 9	2	NM_001253829.2	ENSP00000477817.1
PTPDC1	ENST00000288976.3	c.341C>T	p.Ala114Val	missense_variant	Exon 2 of 9	1		ENSP00000288976.3
PTPDC1	ENST00000375360.7	c.185C>T	p.Ala62Val	missense_variant	Exon 3 of 10	1		ENSP00000364509.3
PTPDC1	ENST00000650567.1	c.185C>T	p.Ala62Val	missense_variant	Exon 4 of 11			ENSP00000497158.1

Frequencies

GnomAD3 genomes AF: 0.0000854 AC: 13 AN: 152166 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000795 AC: 20 AN: 251492 Hom.: 0 AF XY: 0.0000662 AC XY: 9 AN XY: 135920

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000869 AC: 127 AN: 1461886 Hom.: 0 Cov.: 31 AF XY: 0.0000811 AC XY: 59 AN XY: 727242

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000108

Gnomad4 OTH exome AF: 0.0000993

GnomAD4 genome AF: 0.0000854 AC: 13 AN: 152166 Hom.: 0 Cov.: 33 AF XY: 0.000108 AC XY: 8 AN XY: 74336

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000176

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000223 Hom.: 0

Bravo AF: 0.0000604

ExAC AF: 0.0000247 AC: 3

EpiCase AF: 0.000109

EpiControl AF: 0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 07, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.341C>T (p.A114V) alteration is located in exon 2 (coding exon 2) of the PTPDC1 gene. This alteration results from a C to T substitution at nucleotide position 341, causing the alanine (A) at amino acid position 114 to be replaced by a valine (V). 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	0.37
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.24
CADD	Pathogenic	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.16	T;T;T;.
Eigen	Pathogenic	0.69
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Pathogenic	0.97	.;D;D;D
M_CAP	Benign	0.021	T
MetaRNN	Uncertain	0.51	D;D;D;D
MetaSVM	Benign	-0.42	T
MutationAssessor	Uncertain	2.5	M;M;.;.
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-2.2	N;.;.;N
REVEL	Uncertain	0.30
Sift	Benign	0.098	T;.;.;D
Sift4G	Benign	0.27	T;.;T;T
Polyphen		0.99	D;D;.;D
Vest4		0.62
MutPred		0.69		Loss of ubiquitination at K64 (P = 0.0506);Loss of ubiquitination at K64 (P = 0.0506);.;.;
MVP		0.83
MPC		0.47
ClinPred		0.37	T
GERP RS		5.5
Varity_R		0.15
gMVP		0.72

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

Other links and lift over

dbSNP: rs567274018; hg19: chr9-96847635;