9-94085370-C-A

Position:

• chr9-94085370-C-A

Variant summary

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

The NM_001253829.2(PTPDC1):​c.364C>A​(p.Pro122Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: PTPDC1 NM_001253829.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.63

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/exons	MANE	UniProt
PTPDC1	NM_001253829.2	c.364C>A	p.Pro122Thr	missense_variant	2/9	ENST00000620992.5
PTPDC1	NM_152422.4	c.358C>A	p.Pro120Thr	missense_variant	2/9
PTPDC1	NM_177995.3	c.202C>A	p.Pro68Thr	missense_variant	3/10
PTPDC1	NM_001253830.2	c.202C>A	p.Pro68Thr	missense_variant	3/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPDC1	ENST00000620992.5	c.364C>A	p.Pro122Thr	missense_variant	2/9	2	NM_001253829.2
PTPDC1	ENST00000288976.3	c.358C>A	p.Pro120Thr	missense_variant	2/9	1
PTPDC1	ENST00000375360.7	c.202C>A	p.Pro68Thr	missense_variant	3/10	1		P1
PTPDC1	ENST00000650567.1	c.202C>A	p.Pro68Thr	missense_variant	4/11			P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 10, 2024

The c.358C>A (p.P120T) alteration is located in exon 2 (coding exon 2) of the PTPDC1 gene. This alteration results from a C to A substitution at nucleotide position 358, causing the proline (P) at amino acid position 120 to be replaced by a threonine (T). 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	0.26
BayesDel_addAF	Uncertain	0.059	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T;T;T;.
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.97	.;D;D;D
M_CAP	Benign	0.059	D
MetaRNN	Uncertain	0.66	D;D;D;D
MetaSVM	Uncertain	-0.26	T
MutationAssessor	Uncertain	2.8	M;M;.;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.51	T
PROVEAN	Pathogenic	-4.7	D;.;.;D
REVEL	Uncertain	0.38
Sift	Uncertain	0.029	D;.;.;D
Sift4G	Uncertain	0.012	D;.;D;D
Polyphen		0.98	D;D;.;P
Vest4		0.61
MutPred		0.45		Loss of ubiquitination at K64 (P = 0.0573);Loss of ubiquitination at K64 (P = 0.0573);.;.;
MVP		0.76
MPC		0.45
ClinPred		0.99	D
GERP RS		3.6
Varity_R		0.52
gMVP		0.77

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-96847652;