rs150238247

Variant names:

• chr9-94095325-T-A
• rs150238247
• NM_001253829.2:c.625T>A

Your query was ambiguous. Multiple possible variants found:

• chr9-94095325-T-A
• chr9-94095325-T-C
• chr9-94095325-T-G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001253829.2(PTPDC1):​c.625T>A​(p.Tyr209Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,448,134 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 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. Y209D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PTPDC1 NM_001253829.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.43
• Publications: 0 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.867

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPDC1	NM_001253829.2	c.625T>A	p.Tyr209Asn	missense_variant	Exon 5 of 9	ENST00000620992.5	NP_001240758.1
PTPDC1	NM_152422.4	c.619T>A	p.Tyr207Asn	missense_variant	Exon 5 of 9		NP_689635.3
PTPDC1	NM_177995.3	c.463T>A	p.Tyr155Asn	missense_variant	Exon 6 of 10		NP_818931.1
PTPDC1	NM_001253830.2	c.463T>A	p.Tyr155Asn	missense_variant	Exon 6 of 10		NP_001240759.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPDC1	ENST00000620992.5	c.625T>A	p.Tyr209Asn	missense_variant	Exon 5 of 9	2	NM_001253829.2	ENSP00000477817.1
PTPDC1	ENST00000288976.3	c.619T>A	p.Tyr207Asn	missense_variant	Exon 5 of 9	1		ENSP00000288976.3
PTPDC1	ENST00000375360.7	c.463T>A	p.Tyr155Asn	missense_variant	Exon 6 of 10	1		ENSP00000364509.3
PTPDC1	ENST00000650567.1	c.463T>A	p.Tyr155Asn	missense_variant	Exon 7 of 11			ENSP00000497158.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1448134 Hom.: 0 Cov.: 30 AF XY: 0.00000139 AC XY: 1 AN XY: 720046

African (AFR) AF: 0.00 AC: 0 AN: 32702

American (AMR) AF: 0.00 AC: 0 AN: 41098

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25538

East Asian (EAS) AF: 0.00 AC: 0 AN: 39632

South Asian (SAS) AF: 0.00 AC: 0 AN: 82872

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53298

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5702

European-Non Finnish (NFE) AF: 0.00000181 AC: 2 AN: 1107348

Other (OTH) AF: 0.00 AC: 0 AN: 59944

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Uncertain	0.13
CADD	Pathogenic	29
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.45	T;T;T;.
Eigen	Pathogenic	0.76
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Pathogenic	0.98	.;D;D;D
M_CAP	Benign	0.044	D
MetaRNN	Pathogenic	0.87	D;D;D;D
MetaSVM	Benign	-0.77	T
MutationAssessor	Pathogenic	3.6	H;H;.;.
PhyloP100		7.4
PrimateAI	Pathogenic	0.86	D
PROVEAN	Pathogenic	-8.0	D;.;.;D
REVEL	Uncertain	0.62
Sift	Pathogenic	0.0	D;.;.;D
Sift4G	Pathogenic	0.0	D;.;D;D
Polyphen		1.0	D;D;.;D
Vest4		0.96
MutPred		0.70		Loss of stability (P = 0.0536);Loss of stability (P = 0.0536);.;.;
MVP		0.60
MPC		0.77
ClinPred		1.0	D
GERP RS		5.7
Varity_R		0.94
gMVP		0.93
Mutation Taster		=9/91	disease causing

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

Other links and lift over

dbSNP: rs150238247; hg19: chr9-96857607;