rs752526834

Variant names:

• chr9-94084666-G-A
• rs752526834
• NM_001253829.2:c.136G>A

Your query was ambiguous. Multiple possible variants found:

• chr9-94084666-G-A
• chr9-94084666-G-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001253829.2(PTPDC1):​c.136G>A​(p.Gly46Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000806 in 1,613,522 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000075 (0 hom.)
• Consequence: PTPDC1 NM_001253829.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0130
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.049378425).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPDC1	NM_001253829.2	c.136G>A	p.Gly46Ser	missense_variant	Exon 1 of 9	ENST00000620992.5	NP_001240758.1
PTPDC1	NM_152422.4	c.136G>A	p.Gly46Ser	missense_variant	Exon 1 of 9		NP_689635.3
PTPDC1	NM_177995.3	c.83-585G>A		intron_variant	Intron 2 of 9		NP_818931.1
PTPDC1	NM_001253830.2	c.83-585G>A		intron_variant	Intron 2 of 9		NP_001240759.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPDC1	ENST00000620992.5	c.136G>A	p.Gly46Ser	missense_variant	Exon 1 of 9	2	NM_001253829.2	ENSP00000477817.1
PTPDC1	ENST00000288976.3	c.136G>A	p.Gly46Ser	missense_variant	Exon 1 of 9	1		ENSP00000288976.3
PTPDC1	ENST00000375360.7	c.83-585G>A		intron_variant	Intron 2 of 9	1		ENSP00000364509.3
PTPDC1	ENST00000650567.1	c.83-585G>A		intron_variant	Intron 3 of 10			ENSP00000497158.1

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152212 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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000280 AC: 7 AN: 249570 AF XY: 0.0000148

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000534

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000753 AC: 11 AN: 1461310 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 726960

African (AFR) AF: 0.00 AC: 0 AN: 33436

American (AMR) AF: 0.0000224 AC: 1 AN: 44688

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26110

East Asian (EAS) AF: 0.00 AC: 0 AN: 39662

South Asian (SAS) AF: 0.00 AC: 0 AN: 86230

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53272

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00000899 AC: 10 AN: 1111772

Other (OTH) AF: 0.00 AC: 0 AN: 60376

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152212 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74372

African (AFR) AF: 0.0000241 AC: 1 AN: 41444

American (AMR) AF: 0.00 AC: 0 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68040

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000658 Hom.: 0

Bravo AF: 0.0000227

ExAC AF: 0.0000330 AC: 4

EpiCase AF: 0.00

EpiControl AF: 0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 12, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.136G>A (p.G46S) alteration is located in exon 1 (coding exon 1) of the PTPDC1 gene. This alteration results from a G to A substitution at nucleotide position 136, causing the glycine (G) at amino acid position 46 to be replaced by a serine (S). 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
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.7
DANN	Benign	0.93
DEOGEN2	Benign	0.0094	T;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.51	T;T
M_CAP	Benign	0.0027	T
MetaRNN	Benign	0.049	T;T
MetaSVM	Benign	-0.93	T
PhyloP100		0.013
PrimateAI	Benign	0.31	T
PROVEAN	Benign	0.43	.;N
REVEL	Benign	0.020
Sift	Benign	0.39	.;T
Polyphen		0.021	.;B
Vest4		0.19
MVP		0.030
MPC		0.13
ClinPred		0.043	T
GERP RS		0.33
PromoterAI		-0.016	Neutral
gMVP		0.44
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs752526834; hg19: chr9-96846948;