chr9-94088147-A-C

Variant names:

• chr9-94088147-A-C
• rs758549300
• NM_001253829.2:c.500A>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001253829.2(PTPDC1):​c.500A>C​(p.His167Pro) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. 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. H167R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PTPDC1 NM_001253829.2 missense, splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.83
• Publications: 1 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3882991).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPDC1	NM_001253829.2	c.500A>C	p.His167Pro	missense_variant, splice_region_variant	Exon 4 of 9	ENST00000620992.5	NP_001240758.1
PTPDC1	NM_152422.4	c.494A>C	p.His165Pro	missense_variant, splice_region_variant	Exon 4 of 9		NP_689635.3
PTPDC1	NM_177995.3	c.338A>C	p.His113Pro	missense_variant, splice_region_variant	Exon 5 of 10		NP_818931.1
PTPDC1	NM_001253830.2	c.338A>C	p.His113Pro	missense_variant, splice_region_variant	Exon 5 of 10		NP_001240759.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPDC1	ENST00000620992.5	c.500A>C	p.His167Pro	missense_variant, splice_region_variant	Exon 4 of 9	2	NM_001253829.2	ENSP00000477817.1
PTPDC1	ENST00000288976.3	c.494A>C	p.His165Pro	missense_variant, splice_region_variant	Exon 4 of 9	1		ENSP00000288976.3
PTPDC1	ENST00000375360.7	c.338A>C	p.His113Pro	missense_variant, splice_region_variant	Exon 5 of 10	1		ENSP00000364509.3
PTPDC1	ENST00000650567.1	c.338A>C	p.His113Pro	missense_variant, splice_region_variant	Exon 6 of 11			ENSP00000497158.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000400 AC: 1 AN: 249972 AF XY: 0.00000740

Gnomad AFR exome AF: 0.00

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: 0.00000883

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.49
BayesDel_addAF	Uncertain	0.015	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	20
DANN	Benign	0.97
DEOGEN2	Benign	0.19	T;T;T;.
Eigen	Benign	0.083
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.91	.;D;D;D
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.39	T;T;T;T
MetaSVM	Benign	-0.83	T
MutationAssessor	Uncertain	2.2	M;M;.;.
PhyloP100		1.8
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-2.0	N;.;.;N
REVEL	Uncertain	0.34
Sift	Benign	0.20	T;.;.;T
Sift4G	Benign	0.20	T;.;T;T
Polyphen		0.31	B;B;.;B
Vest4		0.56
MutPred		0.64		Gain of relative solvent accessibility (P = 0.0905);Gain of relative solvent accessibility (P = 0.0905);.;.;
MVP		0.69
MPC		0.33
ClinPred		0.45	T
GERP RS		3.6
Varity_R		0.16
gMVP		0.94
Mutation Taster		=81/19	polymorphism

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: rs758549300; hg19: chr9-96850429;