6-63578936-G-C

Position:

• chr6-63578936-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_003463.5(PTP4A1):​c.237G>C​(p.Gln79His) variant causes a missense change. The variant allele was found at a frequency of 0.000000691 in 1,447,104 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: PTP4A1 NM_003463.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.28

Genes affected

PTP4A1 (HGNC:9634): (protein tyrosine phosphatase 4A1) This gene encodes a member of a small class of prenylated protein tyrosine phosphatases (PTPs), which contain a PTP domain and a characteristic C-terminal prenylation motif. The encoded protein is a cell signaling molecule that plays regulatory roles in a variety of cellular processes, including cell proliferation and migration. The protein may also be involved in cancer development and metastasis. This tyrosine phosphatase is a nuclear protein, but may associate with plasma membrane by means of its prenylation motif. Pseudogenes related to this gene are located on chromosomes 1, 2, 5, 7, 11 and X. [provided by RefSeq, Jun 2013]

(HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36984634).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTP4A1	NM_003463.5	c.237G>C	p.Gln79His	missense_variant	4/6	ENST00000626021.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTP4A1	ENST00000626021.3	c.237G>C	p.Gln79His	missense_variant	4/6	1	NM_003463.5	P1
	ENST00000370651.8	c.*586G>C		3_prime_UTR_variant	4/6	1		P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.91e-7 AC: 1 AN: 1447104 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 719792

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.03e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 15, 2022

The c.237G>C (p.Q79H) alteration is located in exon 4 (coding exon 3) of the PTP4A1 gene. This alteration results from a G to C substitution at nucleotide position 237, causing the glutamine (Q) at amino acid position 79 to be replaced by a histidine (H). 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	Benign	0.26
BayesDel_addAF	Uncertain	0.088	D
BayesDel_noAF	Benign	-0.11
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.37	T;T;.
Eigen	Benign	-0.15
Eigen_PC	Benign	0.022
FATHMM_MKL	Pathogenic	0.97	D
M_CAP	Benign	0.045	D
MetaRNN	Benign	0.37	T;T;T
MetaSVM	Benign	-0.65	T
MutationAssessor	Benign	1.4	L;L;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.77	T
Polyphen		0.0080	B;B;.
Vest4		0.60, 0.59
MutPred		0.36		Gain of catalytic residue at D82 (P = 0.0645);Gain of catalytic residue at D82 (P = 0.0645);Gain of catalytic residue at D82 (P = 0.0645);
MVP		0.51
ClinPred		0.62	D
GERP RS		4.0
Varity_R		0.47
gMVP		0.72

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

LitVar

Other links and lift over

dbSNP: rs1778042801; hg19: chr6-64288841;