11-18783387-A-G

Variant names:

• chr11-18783387-A-G
• rs4757718
• NM_006906.2:c.-114+8138T>C

Variant summary

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

The NM_006906.2(PTPN5):​c.-114+8138T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.406 in 152,096 control chromosomes in the GnomAD database, including 13,206 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 0.41 (13206 hom., cov: 32)
• Consequence: PTPN5 NM_006906.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.831
• Publications: 9 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 (EAS) allele frequency at 95% confidence interval = 0.715 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPN5	NM_006906.2	MANE Select	c.-114+8138T>C		intron	N/A	NP_008837.1	P54829-1
	PTPN5	NM_032781.4		c.-69+8138T>C		intron	N/A	NP_116170.3
	PTPN5	NM_001278238.2		c.-53+8138T>C		intron	N/A	NP_001265167.1	P54829-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPN5	ENST00000358540.7	TSL:1 MANE Select	c.-114+8138T>C		intron	N/A	ENSP00000351342.2	P54829-1
	PTPN5	ENST00000396168.1	TSL:1	c.-53+8138T>C		intron	N/A	ENSP00000379471.1	P54829-3
	PTPN5	ENST00000935333.1		c.-114+8138T>C		intron	N/A	ENSP00000605392.1

Frequencies

GnomAD3 genomes AF: 0.406 AC: 61648 AN: 151978 Hom.: 13193 Cov.: 32

Gnomad AFR AF: 0.455

Gnomad AMI AF: 0.190

Gnomad AMR AF: 0.497

Gnomad ASJ AF: 0.394

Gnomad EAS AF: 0.735

Gnomad SAS AF: 0.495

Gnomad FIN AF: 0.377

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.332

Gnomad OTH AF: 0.401

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

GnomAD4 genome AF: 0.406 AC: 61704 AN: 152096 Hom.: 13206 Cov.: 32 AF XY: 0.414 AC XY: 30789 AN XY: 74362

African (AFR) AF: 0.454 AC: 18836 AN: 41484

American (AMR) AF: 0.498 AC: 7621 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.394 AC: 1368 AN: 3470

East Asian (EAS) AF: 0.734 AC: 3787 AN: 5156

South Asian (SAS) AF: 0.496 AC: 2391 AN: 4820

European-Finnish (FIN) AF: 0.377 AC: 3994 AN: 10586

Middle Eastern (MID) AF: 0.422 AC: 124 AN: 294

European-Non Finnish (NFE) AF: 0.332 AC: 22557 AN: 67952

Other (OTH) AF: 0.403 AC: 853 AN: 2116

Alfa AF: 0.364 Hom.: 20633

Bravo AF: 0.418

Asia WGS AF: 0.588 AC: 2045 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.1
DANN	Benign	0.73
PhyloP100		0.83
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: rs4757718; hg19: chr11-18804934;