1-31919061-T-C

Variant names:

• chr1-31919061-T-C
• NM_080391.4:c.5A>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_080391.4(PTP4A2):​c.5A>G​(p.Asn2Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: PTP4A2 NM_080391.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.95

Genes affected

PTP4A2 (HGNC:9635): (protein tyrosine phosphatase 4A2) The protein encoded by this gene belongs to a small class of the protein tyrosine phosphatase (PTP) family. PTPs are cell signaling molecules that play regulatory roles in a variety of cellular processes. PTPs in this class contain a protein tyrosine phosphatase catalytic domain and a characteristic C-terminal prenylation motif. This PTP has been shown to primarily associate with plasmic and endosomal membrane through its C-terminal prenylation. This PTP was found to interact with the beta-subunit of Rab geranylgeranyltransferase II (beta GGT II), and thus may function as a regulator of GGT II activity. Overexpression of this gene in mammalian cells conferred a transformed phenotype, which suggested its role in tumorigenesis. Alternatively spliced transcript variants have been described. Related pseudogenes exist on chromosomes 11, 12 and 17. [provided by RefSeq, Aug 2010]

ENSG00000269967 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTP4A2	NM_080391.4	c.5A>G	p.Asn2Ser	missense_variant	Exon 2 of 6	ENST00000647444.2	NP_536316.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTP4A2	ENST00000647444.2	c.5A>G	p.Asn2Ser	missense_variant	Exon 2 of 6		NM_080391.4	ENSP00000493688.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 24

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 29, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.5A>G (p.N2S) alteration is located in exon 2 (coding exon 1) of the PTP4A2 gene. This alteration results from a A to G substitution at nucleotide position 5, causing the asparagine (N) at amino acid position 2 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
AlphaMissense	Uncertain	0.46
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.030
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.029	T;T;T;.;.;T;T;T;T;.
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	.;.;D;D;D;D;D;D;D;D
M_CAP	Uncertain	0.10	D
MetaRNN	Uncertain	0.70	D;D;D;D;D;D;D;D;D;D
MetaSVM	Uncertain	0.78	D
MutationAssessor	Benign	1.9	L;L;L;L;L;.;.;.;.;.
PrimateAI	Pathogenic	0.82	D
PROVEAN	Uncertain	-2.9	.;.;.;D;.;D;.;.;D;D
REVEL	Uncertain	0.61
Sift	Benign	0.062	.;.;.;T;.;T;.;.;T;.
Sift4G	Benign	0.11	T;.;.;T;T;T;T;T;T;D
Polyphen		0.016	B;B;B;.;.;.;.;.;.;.
Vest4		0.62
MutPred		0.60		Gain of phosphorylation at N2 (P = 0.0163);Gain of phosphorylation at N2 (P = 0.0163);Gain of phosphorylation at N2 (P = 0.0163);Gain of phosphorylation at N2 (P = 0.0163);Gain of phosphorylation at N2 (P = 0.0163);Gain of phosphorylation at N2 (P = 0.0163);Gain of phosphorylation at N2 (P = 0.0163);Gain of phosphorylation at N2 (P = 0.0163);Gain of phosphorylation at N2 (P = 0.0163);Gain of phosphorylation at N2 (P = 0.0163);
MVP		0.73
ClinPred		0.94	D
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.70
gMVP		0.80

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-32384662;