chr6-63559942-G-A

Position:

• chr6-63559942-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001385254.1(PTP4A1):​c.-445-16494G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 151,838 control chromosomes in the GnomAD database, including 5,748 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 0.25 (5748 hom., cov: 31)
• Consequence: PTP4A1 NM_001385254.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.277

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]

PTP4A1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.329 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTP4A1	NM_001385254.1	c.-445-16494G>A		intron_variant			NP_001372183.1
PTP4A1	NM_001385255.1	c.-446+9449G>A		intron_variant			NP_001372184.1
PTP4A1	NM_001385256.1	c.-445-16494G>A		intron_variant			NP_001372185.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTP4A1	ENST00000648894.1	c.-445-16494G>A		intron_variant				ENSP00000497588.1
PTP4A1	ENST00000639568.2	c.-446+9449G>A		intron_variant		5		ENSP00000497431.1
PTP4A1	ENST00000470661.1	n.333-16494G>A		intron_variant		2
ENSG00000289911	ENST00000701584.1	n.133+6156C>T		intron_variant

Frequencies

GnomAD3 genomes AF: 0.253 AC: 38446 AN: 151720 Hom.: 5741 Cov.: 31

Gnomad AFR AF: 0.0852

Gnomad AMI AF: 0.413

Gnomad AMR AF: 0.337

Gnomad ASJ AF: 0.275

Gnomad EAS AF: 0.250

Gnomad SAS AF: 0.303

Gnomad FIN AF: 0.247

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.331

Gnomad OTH AF: 0.276

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

GnomAD4 genome AF: 0.253 AC: 38452 AN: 151838 Hom.: 5748 Cov.: 31 AF XY: 0.253 AC XY: 18768 AN XY: 74184

Gnomad4 AFR AF: 0.0850

Gnomad4 AMR AF: 0.337

Gnomad4 ASJ AF: 0.275

Gnomad4 EAS AF: 0.249

Gnomad4 SAS AF: 0.305

Gnomad4 FIN AF: 0.247

Gnomad4 NFE AF: 0.331

Gnomad4 OTH AF: 0.273

Alfa AF: 0.286 Hom.: 2885

Bravo AF: 0.253

Asia WGS AF: 0.249 AC: 864 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.6
DANN	Benign	0.60

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6916092; hg19: chr6-64269847;