9-94084751-C-T

Variant names:

• chr9-94084751-C-T
• rs1356761508
• NM_001253829.2:c.221C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_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. 14/20 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.77
• Publications: 2 publications found

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

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).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001253829.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPDC1	NM_001253829.2	MANE Select	c.221C>T	p.Thr74Ile	missense	Exon 1 of 9	NP_001240758.1	A0A087WTF0
	PTPDC1	NM_152422.4		c.221C>T	p.Thr74Ile	missense	Exon 1 of 9	NP_689635.3	A2A3K4-2
	PTPDC1	NM_177995.3		c.83-500C>T		intron	N/A	NP_818931.1	A2A3K4-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPDC1	ENST00000620992.5	TSL:2 MANE Select	c.221C>T	p.Thr74Ile	missense	Exon 1 of 9	ENSP00000477817.1	A0A087WTF0
	PTPDC1	ENST00000288976.3	TSL:1	c.221C>T	p.Thr74Ile	missense	Exon 1 of 9	ENSP00000288976.3	A2A3K4-2
	PTPDC1	ENST00000375360.7	TSL:1	c.83-500C>T		intron	N/A	ENSP00000364509.3	A2A3K4-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000280 AC: 4 AN: 1427480 Hom.: 0 Cov.: 30 AF XY: 0.00000424 AC XY: 3 AN XY: 708030

African (AFR) AF: 0.00 AC: 0 AN: 31750

American (AMR) AF: 0.00 AC: 0 AN: 36466

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23976

East Asian (EAS) AF: 0.00 AC: 0 AN: 39286

South Asian (SAS) AF: 0.00 AC: 0 AN: 80906

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52630

Middle Eastern (MID) AF: 0.000179 AC: 1 AN: 5590

European-Non Finnish (NFE) AF: 0.00000273 AC: 3 AN: 1098130

Other (OTH) AF: 0.00 AC: 0 AN: 58746

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0065	T
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.092
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.0096	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.0	T
PhyloP100		2.8
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.25	N
REVEL	Benign	0.042
Sift	Uncertain	0.0020	D
Sift4G	Benign	0.11	T
Polyphen		0.091	B
Vest4		0.27
MutPred		0.16		Gain of catalytic residue at P76 (P = 0.0309)
MVP		0.35
MPC		0.15
ClinPred		0.98	D
GERP RS		4.8
PromoterAI		0.028	Neutral
gMVP		0.56
Mutation Taster		=94/6	polymorphism

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

Other links and lift over

dbSNP: rs1356761508; hg19: chr9-96847033;