6-63544114-T-G

Variant names:

• chr6-63544114-T-G
• rs1322416
• NM_001385254.1:c.-446+16030T>G

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+16030T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.536 in 151,980 control chromosomes in the GnomAD database, including 23,607 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 0.54 (23607 hom., cov: 32)
• Consequence: PTP4A1 NM_001385254.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.94
• Publications: 4 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]

ENSG00000289911 (HGNC:):

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.758 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTP4A1	NM_001385254.1		c.-446+16030T>G		intron	N/A	NP_001372183.1
	PTP4A1	NM_001385255.1		c.-639-6186T>G		intron	N/A	NP_001372184.1
	PTP4A1	NM_001385256.1		c.-446+11584T>G		intron	N/A	NP_001372185.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTP4A1	ENST00000648894.1		c.-446+11584T>G		intron	N/A	ENSP00000497588.1
	PTP4A1	ENST00000639568.2	TSL:5	c.-639-6186T>G		intron	N/A	ENSP00000497431.1
	PTP4A1	ENST00000470661.1	TSL:2	n.332+16030T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.536 AC: 81403 AN: 151864 Hom.: 23545 Cov.: 32

Gnomad AFR AF: 0.765

Gnomad AMI AF: 0.546

Gnomad AMR AF: 0.534

Gnomad ASJ AF: 0.374

Gnomad EAS AF: 0.447

Gnomad SAS AF: 0.501

Gnomad FIN AF: 0.399

Gnomad MID AF: 0.455

Gnomad NFE AF: 0.438

Gnomad OTH AF: 0.495

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

GnomAD4 genome AF: 0.536 AC: 81530 AN: 151980 Hom.: 23607 Cov.: 32 AF XY: 0.534 AC XY: 39653 AN XY: 74272

African (AFR) AF: 0.765 AC: 31708 AN: 41444

American (AMR) AF: 0.535 AC: 8149 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.374 AC: 1296 AN: 3466

East Asian (EAS) AF: 0.447 AC: 2312 AN: 5170

South Asian (SAS) AF: 0.502 AC: 2420 AN: 4818

European-Finnish (FIN) AF: 0.399 AC: 4208 AN: 10552

Middle Eastern (MID) AF: 0.466 AC: 136 AN: 292

European-Non Finnish (NFE) AF: 0.438 AC: 29759 AN: 67970

Other (OTH) AF: 0.495 AC: 1045 AN: 2112

Alfa AF: 0.464 Hom.: 8805

Bravo AF: 0.557

Asia WGS AF: 0.462 AC: 1606 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.54
DANN	Benign	0.43
PhyloP100		-1.9

Splicing

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

Other links and lift over

dbSNP: rs1322416; hg19: chr6-64254019;