chr9-94084680-G-C

Variant names:

• chr9-94084680-G-C
• rs748855776
• NM_001253829.2:c.150G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001253829.2(PTPDC1):​c.150G>C​(p.Lys50Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000868 in 1,613,696 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 0.000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: PTPDC1 NM_001253829.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.782
• 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.

• BP4: Computational evidence support a benign effect (MetaRNN=0.072173536).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPDC1	NM_001253829.2	c.150G>C	p.Lys50Asn	missense_variant	Exon 1 of 9	ENST00000620992.5	NP_001240758.1
PTPDC1	NM_152422.4	c.150G>C	p.Lys50Asn	missense_variant	Exon 1 of 9		NP_689635.3
PTPDC1	NM_177995.3	c.83-571G>C		intron_variant	Intron 2 of 9		NP_818931.1
PTPDC1	NM_001253830.2	c.83-571G>C		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.150G>C	p.Lys50Asn	missense_variant	Exon 1 of 9	2	NM_001253829.2	ENSP00000477817.1
PTPDC1	ENST00000288976.3	c.150G>C	p.Lys50Asn	missense_variant	Exon 1 of 9	1		ENSP00000288976.3
PTPDC1	ENST00000375360.7	c.83-571G>C		intron_variant	Intron 2 of 9	1		ENSP00000364509.3
PTPDC1	ENST00000650567.1	c.83-571G>C		intron_variant	Intron 3 of 10			ENSP00000497158.1

Frequencies

GnomAD3 genomes AF: 0.0000657 AC: 10 AN: 152256 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000241

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000120 AC: 3 AN: 249836 AF XY: 0.0000222

Gnomad AFR exome AF: 0.000186

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461440 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727022

African (AFR) AF: 0.000120 AC: 4 AN: 33452

American (AMR) AF: 0.00 AC: 0 AN: 44678

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39668

South Asian (SAS) AF: 0.00 AC: 0 AN: 86224

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53342

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111818

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

GnomAD4 genome AF: 0.0000657 AC: 10 AN: 152256 Hom.: 0 Cov.: 33 AF XY: 0.0000807 AC XY: 6 AN XY: 74388

African (AFR) AF: 0.000241 AC: 10 AN: 41472

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68046

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

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000718

ExAC AF: 0.00000824 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 05, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.150G>C (p.K50N) alteration is located in exon 1 (coding exon 1) of the PTPDC1 gene. This alteration results from a G to C substitution at nucleotide position 150, causing the lysine (K) at amino acid position 50 to be replaced by an asparagine (N). 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	-0.60	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	20
DANN	Benign	0.97
DEOGEN2	Benign	0.0099	T;.
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.42	T;T
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.072	T;T
MetaSVM	Benign	-0.98	T
PhyloP100		0.78
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.090	.;N
REVEL	Benign	0.031
Sift	Uncertain	0.016	.;D
Sift4G	Benign	0.064	T;T
Polyphen		0.023	.;B
Vest4		0.26
MutPred		0.15		Loss of ubiquitination at K50 (P = 0.0074);Loss of ubiquitination at K50 (P = 0.0074);
MVP		0.10
MPC		0.16
ClinPred		0.22	T
GERP RS		0.85
PromoterAI		0.0042	Neutral
gMVP		0.50
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs748855776; hg19: chr9-96846962;