rs2278732

Variant names:

• chr11-18742566-G-A
• rs2278732
• NM_006906.2:c.484-63C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006906.2(PTPN5):​c.484-63C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.363 in 1,586,526 control chromosomes in the GnomAD database, including 109,551 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 0.30 (8203 hom., cov: 31)
  • Exomes 𝑓: 0.37 (101348 hom.)
• Consequence: PTPN5 NM_006906.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.266
• Publications: 7 publications found

Genes affected

PTPN5 (HGNC:9657): (protein tyrosine phosphatase non-receptor type 5) Enables phosphotyrosine residue binding activity. Predicted to be involved in peptidyl-tyrosine dephosphorylation. Predicted to act upstream of or within protein dephosphorylation. Predicted to be located in nucleoplasm. Predicted to be integral component of membrane. Biomarker of Alzheimer's disease. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.429 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPN5	NM_006906.2	c.484-63C>T		intron_variant	Intron 6 of 14	ENST00000358540.7	NP_008837.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPN5	ENST00000358540.7	c.484-63C>T		intron_variant	Intron 6 of 14	1	NM_006906.2	ENSP00000351342.2

Frequencies

GnomAD3 genomes AF: 0.299 AC: 45305 AN: 151664 Hom.: 8207 Cov.: 31

Gnomad AFR AF: 0.0853

Gnomad AMI AF: 0.498

Gnomad AMR AF: 0.438

Gnomad ASJ AF: 0.475

Gnomad EAS AF: 0.296

Gnomad SAS AF: 0.419

Gnomad FIN AF: 0.291

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.377

Gnomad OTH AF: 0.338

GnomAD4 exome AF: 0.370 AC: 531064 AN: 1434744 Hom.: 101348 AF XY: 0.373 AC XY: 265659 AN XY: 711960

African (AFR) AF: 0.0736 AC: 2447 AN: 33226

American (AMR) AF: 0.512 AC: 22436 AN: 43788

Ashkenazi Jewish (ASJ) AF: 0.476 AC: 11896 AN: 25016

East Asian (EAS) AF: 0.285 AC: 11252 AN: 39440

South Asian (SAS) AF: 0.424 AC: 35432 AN: 83486

European-Finnish (FIN) AF: 0.305 AC: 13316 AN: 43620

Middle Eastern (MID) AF: 0.438 AC: 1871 AN: 4268

European-Non Finnish (NFE) AF: 0.373 AC: 410874 AN: 1102424

Other (OTH) AF: 0.362 AC: 21540 AN: 59476

GnomAD4 genome AF: 0.298 AC: 45307 AN: 151782 Hom.: 8203 Cov.: 31 AF XY: 0.299 AC XY: 22159 AN XY: 74158

African (AFR) AF: 0.0852 AC: 3532 AN: 41434

American (AMR) AF: 0.438 AC: 6672 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.475 AC: 1649 AN: 3470

East Asian (EAS) AF: 0.296 AC: 1525 AN: 5146

South Asian (SAS) AF: 0.420 AC: 2009 AN: 4788

European-Finnish (FIN) AF: 0.291 AC: 3068 AN: 10532

Middle Eastern (MID) AF: 0.398 AC: 117 AN: 294

European-Non Finnish (NFE) AF: 0.377 AC: 25579 AN: 67860

Other (OTH) AF: 0.334 AC: 703 AN: 2102

Alfa AF: 0.378 Hom.: 16017

Bravo AF: 0.302

Asia WGS AF: 0.303 AC: 1054 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.7
DANN	Benign	0.61
PhyloP100		-0.27
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2278732; hg19: chr11-18764113;