chr6-63580063-G-T

Variant names:

• chr6-63580063-G-T
• rs1618240
• NM_003463.5:c.411G>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001385265.1(PTP4A1):​c.407G>T​(p.Gly136Val) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00316 in 1,608,658 control chromosomes in the GnomAD database, including 136 homozygotes. In-silico tool predicts a benign outcome for this variant. 5/6 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.017 (76 hom., cov: 32)
  • Exomes 𝑓: 0.0017 (60 hom.)
• Consequence: PTP4A1 NM_001385265.1 missense, splice_region
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0170
• Publications: 1 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: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP6: Variant 6-63580063-G-T is Benign according to our data. Variant chr6-63580063-G-T is described in ClinVar as Benign. ClinVar VariationId is 716893.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.057 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001385265.1. 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_003463.5	MANE Select	c.411G>T	p.Arg137Arg	synonymous	Exon 6 of 6	NP_003454.1	Q93096
	LOC128125822	NM_001415059.2	MANE Select	c.*3532G>T		3_prime_UTR	Exon 2 of 2	NP_001401988.1	A0A3F2YNX1
	PTP4A1	NM_001385266.1		c.454G>T	p.Ala152Ser	missense	Exon 6 of 6	NP_001372195.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTP4A1	ENST00000626021.3	TSL:1 MANE Select	c.411G>T	p.Arg137Arg	synonymous	Exon 6 of 6	ENSP00000485687.1	Q93096
	ENSG00000285976	ENST00000715520.1	MANE Select	c.*3532G>T		3_prime_UTR	Exon 2 of 2	ENSP00000520460.1	A0A3F2YNX1
	ENSG00000285976	ENST00000370651.8	TSL:1	c.*760G>T		3_prime_UTR	Exon 6 of 6	ENSP00000359685.4	A0A3F2YNX1

Frequencies

GnomAD3 genomes AF: 0.0171 AC: 2595 AN: 151378 Hom.: 76 Cov.: 32

Gnomad AFR AF: 0.0590

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00684

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000625

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000236

Gnomad OTH AF: 0.0197

GnomAD2 exomes AF: 0.00476 AC: 1185 AN: 249002 AF XY: 0.00335

Gnomad AFR exome AF: 0.0619

Gnomad AMR exome AF: 0.00384

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000320

Gnomad OTH exome AF: 0.00199

GnomAD4 exome AF: 0.00170 AC: 2484 AN: 1457166 Hom.: 60 Cov.: 31 AF XY: 0.00144 AC XY: 1044 AN XY: 725192

African (AFR) AF: 0.0576 AC: 1912 AN: 33200

American (AMR) AF: 0.00400 AC: 178 AN: 44514

Ashkenazi Jewish (ASJ) AF: 0.0000384 AC: 1 AN: 26034

East Asian (EAS) AF: 0.00 AC: 0 AN: 39666

South Asian (SAS) AF: 0.0000814 AC: 7 AN: 86034

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52584

Middle Eastern (MID) AF: 0.00365 AC: 21 AN: 5758

European-Non Finnish (NFE) AF: 0.000115 AC: 128 AN: 1109192

Other (OTH) AF: 0.00394 AC: 237 AN: 60184

GnomAD4 genome AF: 0.0172 AC: 2601 AN: 151492 Hom.: 76 Cov.: 32 AF XY: 0.0159 AC XY: 1175 AN XY: 74004

African (AFR) AF: 0.0590 AC: 2435 AN: 41290

American (AMR) AF: 0.00683 AC: 104 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.000417 AC: 2 AN: 4798

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10392

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000236 AC: 16 AN: 67844

Other (OTH) AF: 0.0195 AC: 41 AN: 2100

Alfa AF: 0.00517 Hom.: 22

Bravo AF: 0.0193

Asia WGS AF: 0.00404 AC: 14 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.000593

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	10
DANN	Benign	0.85
PhyloP100		-0.017
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=85/15	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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: rs1618240; hg19: chr6-64289968;