6-63576888-G-A

Variant names:

• chr6-63576888-G-A
• NM_003463.5:c.8G>A

Variant summary

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

The NM_003463.5(PTP4A1):​c.8G>A​(p.Arg3Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000548 in 1,459,836 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: 0.0000055 (0 hom.)
• Consequence: PTP4A1 NM_003463.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.69
• Publications: 0 publications found

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]

LOC128125822 (HGNC:0):

ENSG00000285976 (HGNC:):

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=0.35478723).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003463.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTP4A1	NM_003463.5	MANE Select	c.8G>A	p.Arg3Gln	missense	Exon 2 of 6	NP_003454.1	Q93096
	LOC128125822	NM_001415059.2	MANE Select	c.*357G>A		3_prime_UTR	Exon 2 of 2	NP_001401988.1	A0A3F2YNX1
	PTP4A1	NM_001385265.1		c.8G>A	p.Arg3Gln	missense	Exon 2 of 6	NP_001372194.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTP4A1	ENST00000626021.3	TSL:1 MANE Select	c.8G>A	p.Arg3Gln	missense	Exon 2 of 6	ENSP00000485687.1	Q93096
	ENSG00000285976	ENST00000715520.1	MANE Select	c.*357G>A		3_prime_UTR	Exon 2 of 2	ENSP00000520460.1	A0A3F2YNX1
	ENSG00000285976	ENST00000370651.8	TSL:1	c.*357G>A		3_prime_UTR	Exon 2 of 6	ENSP00000359685.4	A0A3F2YNX1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000548 AC: 8 AN: 1459836 Hom.: 0 Cov.: 30 AF XY: 0.00000826 AC XY: 6 AN XY: 726174

African (AFR) AF: 0.00 AC: 0 AN: 33388

American (AMR) AF: 0.00 AC: 0 AN: 44408

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26108

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 85818

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5186

European-Non Finnish (NFE) AF: 0.00000630 AC: 7 AN: 1111596

Other (OTH) AF: 0.00 AC: 0 AN: 60256

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.71
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.030
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.038	T
Eigen	Benign	0.044
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.35	T
MetaSVM	Uncertain	0.013	D
MutationAssessor	Benign	0.69	N
PhyloP100		6.7
PrimateAI	Uncertain	0.74	T
Sift4G	Benign	0.28	T
Polyphen		0.0030	B
Vest4		0.32
MutPred		0.42		Loss of MoRF binding (P = 0.0108)
MVP		0.40
ClinPred		0.66	D
GERP RS		4.8
PromoterAI		-0.011	Neutral
Varity_R		0.16
gMVP		0.77
Mutation Taster		=65/35	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

hg19: chr6-64286793; COSMIC: COSV101037910; COSMIC: COSV101037910;