6-63530611-G-T

Variant names:

• chr6-63530611-G-T
• rs2622274
• NM_001385254.1:c.-446+2527G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001385254.1(PTP4A1):​c.-446+2527G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.467 in 151,760 control chromosomes in the GnomAD database, including 16,811 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.47 (16811 hom., cov: 31)
• Consequence: PTP4A1 NM_001385254.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09
• Publications: 8 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]

LGSN (HGNC:21016): (lengsin, lens protein with glutamine synthetase domain) This gene encodes a protein with similarity to the GS I members of the glutamine synthetase superfamily. The encoded protein is referred to as a pseudo-glutamine synthetase because it has no glutamine synthesis activity and may function as a chaperone protein. This protein is localized to the lens and may be associated with cataract disease. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2009]

ENSG00000289911 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.525 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001385254.1. 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_001385254.1		c.-446+2527G>T		intron	N/A	NP_001372183.1	Q93096
	PTP4A1	NM_001385255.1		c.-640+2527G>T		intron	N/A	NP_001372184.1	Q93096
	PTP4A1	NM_001385256.1		c.-639-1726G>T		intron	N/A	NP_001372185.1	Q93096

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTP4A1	ENST00000648894.1		c.-639-1726G>T		intron	N/A	ENSP00000497588.1	Q93096
	PTP4A1	ENST00000639568.2	TSL:5	c.-640+2527G>T		intron	N/A	ENSP00000497431.1	A0A3B3ISR8
	PTP4A1	ENST00000470661.1	TSL:2	n.332+2527G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.466 AC: 70727 AN: 151642 Hom.: 16779 Cov.: 31

Gnomad AFR AF: 0.531

Gnomad AMI AF: 0.545

Gnomad AMR AF: 0.507

Gnomad ASJ AF: 0.359

Gnomad EAS AF: 0.451

Gnomad SAS AF: 0.493

Gnomad FIN AF: 0.384

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.435

Gnomad OTH AF: 0.439

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.467 AC: 70815 AN: 151760 Hom.: 16811 Cov.: 31 AF XY: 0.465 AC XY: 34489 AN XY: 74160

African (AFR) AF: 0.531 AC: 21970 AN: 41366

American (AMR) AF: 0.508 AC: 7732 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.359 AC: 1244 AN: 3466

East Asian (EAS) AF: 0.451 AC: 2316 AN: 5140

South Asian (SAS) AF: 0.495 AC: 2385 AN: 4816

European-Finnish (FIN) AF: 0.384 AC: 4030 AN: 10498

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.436 AC: 29584 AN: 67930

Other (OTH) AF: 0.441 AC: 931 AN: 2110

Alfa AF: 0.439 Hom.: 24518

Bravo AF: 0.478

Asia WGS AF: 0.441 AC: 1531 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.16
DANN	Benign	0.38
PhyloP100		-1.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2622274;

hg19: chr6-64240516;