6-63580091-C-T

Variant names:

• chr6-63580091-C-T
• rs1681943
• NM_003463.5:c.439C>T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_003463.5(PTP4A1):​c.439C>T​(p.Leu147Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00366 in 1,609,758 control chromosomes in the GnomAD database, including 183 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.020 (101 hom., cov: 32)
  • Exomes 𝑓: 0.0020 (82 hom.)
• Consequence: PTP4A1 NM_003463.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.67
• Publications: 2 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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP6: Variant 6-63580091-C-T is Benign according to our data. Variant chr6-63580091-C-T is described in ClinVar as Benign. ClinVar VariationId is 716894.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.67 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0669 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003463.5. 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.439C>T	p.Leu147Leu	synonymous	Exon 6 of 6	NP_003454.1	Q93096
	LOC128125822	NM_001415059.2	MANE Select	c.*3560C>T		3_prime_UTR	Exon 2 of 2	NP_001401988.1	A0A3F2YNX1
	PTP4A1	NM_001385265.1		c.435C>T	p.Phe145Phe	synonymous	Exon 6 of 6	NP_001372194.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTP4A1	ENST00000626021.3	TSL:1 MANE Select	c.439C>T	p.Leu147Leu	synonymous	Exon 6 of 6	ENSP00000485687.1	Q93096
	ENSG00000285976	ENST00000715520.1	MANE Select	c.*3560C>T		3_prime_UTR	Exon 2 of 2	ENSP00000520460.1	A0A3F2YNX1
	ENSG00000285976	ENST00000370651.8	TSL:1	c.*788C>T		3_prime_UTR	Exon 6 of 6	ENSP00000359685.4	A0A3F2YNX1

Frequencies

GnomAD3 genomes AF: 0.0199 AC: 2990 AN: 150016 Hom.: 101 Cov.: 32

Gnomad AFR AF: 0.0690

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00784

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000629

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00962

Gnomad NFE AF: 0.000251

Gnomad OTH AF: 0.0213

GnomAD2 exomes AF: 0.00543 AC: 1361 AN: 250482 AF XY: 0.00389

Gnomad AFR exome AF: 0.0711

Gnomad AMR exome AF: 0.00426

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000163

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000327

Gnomad OTH exome AF: 0.00262

GnomAD4 exome AF: 0.00198 AC: 2888 AN: 1459630 Hom.: 82 Cov.: 32 AF XY: 0.00166 AC XY: 1204 AN XY: 726148

African (AFR) AF: 0.0666 AC: 2226 AN: 33408

American (AMR) AF: 0.00457 AC: 204 AN: 44686

Ashkenazi Jewish (ASJ) AF: 0.0000384 AC: 1 AN: 26072

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39664

South Asian (SAS) AF: 0.000128 AC: 11 AN: 86148

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53008

Middle Eastern (MID) AF: 0.00417 AC: 24 AN: 5752

European-Non Finnish (NFE) AF: 0.000123 AC: 137 AN: 1110618

Other (OTH) AF: 0.00465 AC: 280 AN: 60274

GnomAD4 genome AF: 0.0200 AC: 3000 AN: 150128 Hom.: 101 Cov.: 32 AF XY: 0.0187 AC XY: 1368 AN XY: 73130

African (AFR) AF: 0.0690 AC: 2816 AN: 40796

American (AMR) AF: 0.00782 AC: 118 AN: 15080

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3460

East Asian (EAS) AF: 0.00 AC: 0 AN: 5112

South Asian (SAS) AF: 0.000420 AC: 2 AN: 4764

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9954

Middle Eastern (MID) AF: 0.0103 AC: 3 AN: 290

European-Non Finnish (NFE) AF: 0.000251 AC: 17 AN: 67670

Other (OTH) AF: 0.0210 AC: 44 AN: 2092

Alfa AF: 0.0104 Hom.: 19

Bravo AF: 0.0221

Asia WGS AF: 0.00433 AC: 15 AN: 3478

EpiCase AF: 0.000219

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	-0.54
CADD	Benign	5.3
DANN	Benign	0.92
PhyloP100		1.7
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs1681943; hg19: chr6-64289996; COSMIC: COSV65715188; COSMIC: COSV65715188;