6-63580091-C-A

Variant names:

• chr6-63580091-C-A
• rs1681943
• NM_003463.5:c.439C>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.439C>A​(p.Leu147Met) variant causes a missense 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. 11/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L147L) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PTP4A1 NM_003463.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.67
• Publications: 2 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=0.2662199).

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.439C>A	p.Leu147Met	missense	Exon 6 of 6	NP_003454.1	Q93096
	LOC128125822	NM_001415059.2	MANE Select	c.*3560C>A		3_prime_UTR	Exon 2 of 2	NP_001401988.1	A0A3F2YNX1
	PTP4A1	NM_001385265.1		c.435C>A	p.Phe145Leu	missense	Exon 6 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.439C>A	p.Leu147Met	missense	Exon 6 of 6	ENSP00000485687.1	Q93096
	ENSG00000285976	ENST00000715520.1	MANE Select	c.*3560C>A		3_prime_UTR	Exon 2 of 2	ENSP00000520460.1	A0A3F2YNX1
	ENSG00000285976	ENST00000370651.8	TSL:1	c.*788C>A		3_prime_UTR	Exon 6 of 6	ENSP00000359685.4	A0A3F2YNX1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Benign	19
DANN	Benign	0.95
DEOGEN2	Benign	0.063	T
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.41
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.034	D
MetaRNN	Benign	0.27	T
MetaSVM	Uncertain	-0.27	T
MutationAssessor	Benign	1.4	L
PhyloP100		1.7
PrimateAI	Pathogenic	0.83	D
Sift4G	Benign	0.17	T
Polyphen		0.0040	B
Vest4		0.31
MutPred		0.42		Loss of catalytic residue at L147 (P = 0.0423)
MVP		0.32
ClinPred		0.18	T
GERP RS		-0.66
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.6
Varity_R		0.24
gMVP		0.56
Mutation Taster		=68/32	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: rs1681943; hg19: chr6-64289996;