11-18780793-C-T

Variant names:

• chr11-18780793-C-T
• rs10766504
• NM_006906.2:c.-113-8722G>A

Variant summary

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

The NM_006906.2(PTPN5):​c.-113-8722G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.301 in 151,980 control chromosomes in the GnomAD database, including 7,249 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 (7249 hom., cov: 31)
• Consequence: PTPN5 NM_006906.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.13
• Publications: 2 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.334 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006906.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPN5	NM_006906.2	MANE Select	c.-113-8722G>A		intron	N/A	NP_008837.1
	PTPN5	NM_032781.4		c.-68-8767G>A		intron	N/A	NP_116170.3
	PTPN5	NM_001278238.2		c.-53+10732G>A		intron	N/A	NP_001265167.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPN5	ENST00000358540.7	TSL:1 MANE Select	c.-113-8722G>A		intron	N/A	ENSP00000351342.2
	PTPN5	ENST00000396168.1	TSL:1	c.-53+10732G>A		intron	N/A	ENSP00000379471.1
	PTPN5	ENST00000396170.5	TSL:2	c.-68-8767G>A		intron	N/A	ENSP00000379473.1

Frequencies

GnomAD3 genomes AF: 0.301 AC: 45747 AN: 151862 Hom.: 7239 Cov.: 31

Gnomad AFR AF: 0.339

Gnomad AMI AF: 0.399

Gnomad AMR AF: 0.186

Gnomad ASJ AF: 0.218

Gnomad EAS AF: 0.101

Gnomad SAS AF: 0.264

Gnomad FIN AF: 0.338

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.321

Gnomad OTH AF: 0.259

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

GnomAD4 genome AF: 0.301 AC: 45787 AN: 151980 Hom.: 7249 Cov.: 31 AF XY: 0.297 AC XY: 22063 AN XY: 74312

African (AFR) AF: 0.339 AC: 14032 AN: 41408

American (AMR) AF: 0.186 AC: 2836 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.218 AC: 758 AN: 3472

East Asian (EAS) AF: 0.102 AC: 530 AN: 5186

South Asian (SAS) AF: 0.263 AC: 1265 AN: 4806

European-Finnish (FIN) AF: 0.338 AC: 3566 AN: 10546

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.321 AC: 21816 AN: 67970

Other (OTH) AF: 0.261 AC: 552 AN: 2112

Alfa AF: 0.311 Hom.: 11823

Bravo AF: 0.288

Asia WGS AF: 0.213 AC: 742 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.017
DANN	Benign	0.43
PhyloP100		-3.1
Mutation Taster		=100/0	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: rs10766504; hg19: chr11-18802340;