11-18783387-A-G

Position:

• chr11-18783387-A-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPN5	NM_006906.2	c.-114+8138T>C		intron_variant		ENST00000358540.7	NP_008837.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPN5	ENST00000358540.7	c.-114+8138T>C		intron_variant		1	NM_006906.2	ENSP00000351342.2
PTPN5	ENST00000396168.1	c.-53+8138T>C		intron_variant		1		ENSP00000379471.1
PTPN5	ENST00000396170.5	c.-69+8138T>C		intron_variant		2		ENSP00000379473.1

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

Gnomad4 AFR AF: 0.454

Gnomad4 AMR AF: 0.498

Gnomad4 ASJ AF: 0.394

Gnomad4 EAS AF: 0.734

Gnomad4 SAS AF: 0.496

Gnomad4 FIN AF: 0.377

Gnomad4 NFE AF: 0.332

Gnomad4 OTH AF: 0.403

Alfa AF: 0.356 Hom.: 14436

Bravo AF: 0.418

Asia WGS AF: 0.588 AC: 2045 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	7.1
DANN	Benign	0.73

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

Publications

LitVar

Other links and lift over

dbSNP: rs4757718; hg19: chr11-18804934;