6-63525101-T-C

Variant names:

• chr6-63525101-T-C
• rs1197905
• NM_001385254.1:c.-711-2718T>C

Variant summary

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

The NM_001385254.1(PTP4A1):​c.-711-2718T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.535 in 152,028 control chromosomes in the GnomAD database, including 23,622 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 (23622 hom., cov: 32)
• Consequence: PTP4A1 NM_001385254.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.393

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.765 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTP4A1	NM_001385254.1	c.-711-2718T>C		intron_variant	Intron 1 of 6		NP_001372183.1
PTP4A1	NM_001385255.1	c.-905-2718T>C		intron_variant	Intron 2 of 8		NP_001372184.1
PTP4A1	NM_001385256.1	c.-905-2718T>C		intron_variant	Intron 1 of 7		NP_001372185.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTP4A1	ENST00000648894.1	c.-905-2718T>C		intron_variant	Intron 1 of 7			ENSP00000497588.1
PTP4A1	ENST00000639568.2	c.-905-2718T>C		intron_variant	Intron 1 of 3	5		ENSP00000497431.1
PTP4A1	ENST00000470661.1	n.67-2718T>C		intron_variant	Intron 1 of 2	2
ENSG00000289911	ENST00000701584.1	n.133+40997A>G		intron_variant	Intron 1 of 5

Frequencies

GnomAD3 genomes AF: 0.535 AC: 81232 AN: 151910 Hom.: 23559 Cov.: 32

Gnomad AFR AF: 0.772

Gnomad AMI AF: 0.544

Gnomad AMR AF: 0.532

Gnomad ASJ AF: 0.359

Gnomad EAS AF: 0.449

Gnomad SAS AF: 0.482

Gnomad FIN AF: 0.382

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.436

Gnomad OTH AF: 0.493

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

GnomAD4 genome AF: 0.535 AC: 81362 AN: 152028 Hom.: 23622 Cov.: 32 AF XY: 0.531 AC XY: 39445 AN XY: 74300

Gnomad4 AFR AF: 0.772

Gnomad4 AMR AF: 0.533

Gnomad4 ASJ AF: 0.359

Gnomad4 EAS AF: 0.449

Gnomad4 SAS AF: 0.484

Gnomad4 FIN AF: 0.382

Gnomad4 NFE AF: 0.436

Gnomad4 OTH AF: 0.494

Alfa AF: 0.492 Hom.: 3178

Bravo AF: 0.557

Asia WGS AF: 0.452 AC: 1569 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.79
DANN	Benign	0.48

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1197905; hg19: chr6-64235006;