rs4757710

chr11-18754135-A-Cchr11-18754135-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006906.2(PTPN5):c.98-9936T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.664 in 151,898 control chromosomes in the GnomAD database, including 34,233 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 0.66 (34233 hom., cov: 30)
• Consequence: PTPN5 NM_006906.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.121

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=-1.0).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.784 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTPN5	NM_006906.2	c.98-9936T>G		intron_variant		ENST00000358540.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPN5	ENST00000358540.7	c.98-9936T>G		intron_variant		1	NM_006906.2
PTPN5	ENST00000396168.1	c.26-9936T>G		intron_variant		1		P1
PTPN5	ENST00000396170.5	c.98-9936T>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.664 AC: 100810 AN: 151780 Hom.: 34218 Cov.: 30

Gnomad AFR AF: 0.529

Gnomad AMI AF: 0.844

Gnomad AMR AF: 0.764

Gnomad ASJ AF: 0.868

Gnomad EAS AF: 0.795

Gnomad SAS AF: 0.805

Gnomad FIN AF: 0.618

Gnomad MID AF: 0.861

Gnomad NFE AF: 0.695

Gnomad OTH AF: 0.729

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

GnomAD4 genome AF: 0.664 AC: 100874 AN: 151898 Hom.: 34233 Cov.: 30 AF XY: 0.666 AC XY: 49445 AN XY: 74226

Gnomad4 AFR AF: 0.529

Gnomad4 AMR AF: 0.764

Gnomad4 ASJ AF: 0.868

Gnomad4 EAS AF: 0.795

Gnomad4 SAS AF: 0.805

Gnomad4 FIN AF: 0.618

Gnomad4 NFE AF: 0.695

Gnomad4 OTH AF: 0.731

Alfa AF: 0.701 Hom.: 21431

Bravo AF: 0.669

Asia WGS AF: 0.784 AC: 2727 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	1.3
Dann	Benign	0.41

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: rs4757710; hg19: chr11-18775682;