11-18754689-C-T

Variant names:

• chr11-18754689-C-T
• rs10832976
• NM_006906.2:c.98-10490G>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.98-10490G>A 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 151,972 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: 32)
• Consequence: PTPN5 NM_006906.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.826
• Publications: 1 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=-0.98).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.785 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPN5	NM_006906.2	c.98-10490G>A		intron_variant	Intron 3 of 14	ENST00000358540.7	NP_008837.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPN5	ENST00000358540.7	c.98-10490G>A		intron_variant	Intron 3 of 14	1	NM_006906.2	ENSP00000351342.2
PTPN5	ENST00000396168.1	c.26-10490G>A		intron_variant	Intron 2 of 13	1		ENSP00000379471.1
PTPN5	ENST00000396170.5	c.98-10490G>A		intron_variant	Intron 3 of 14	2		ENSP00000379473.1

Frequencies

GnomAD3 genomes AF: 0.664 AC: 100800 AN: 151856 Hom.: 34219 Cov.: 32

Gnomad AFR AF: 0.527

Gnomad AMI AF: 0.845

Gnomad AMR AF: 0.764

Gnomad ASJ AF: 0.868

Gnomad EAS AF: 0.793

Gnomad SAS AF: 0.805

Gnomad FIN AF: 0.620

Gnomad MID AF: 0.861

Gnomad NFE AF: 0.696

Gnomad OTH AF: 0.728

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

GnomAD4 genome AF: 0.664 AC: 100857 AN: 151972 Hom.: 34233 Cov.: 32 AF XY: 0.666 AC XY: 49452 AN XY: 74272

African (AFR) AF: 0.526 AC: 21785 AN: 41402

American (AMR) AF: 0.764 AC: 11690 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.868 AC: 3015 AN: 3472

East Asian (EAS) AF: 0.794 AC: 4100 AN: 5166

South Asian (SAS) AF: 0.806 AC: 3877 AN: 4812

European-Finnish (FIN) AF: 0.620 AC: 6523 AN: 10528

Middle Eastern (MID) AF: 0.861 AC: 253 AN: 294

European-Non Finnish (NFE) AF: 0.696 AC: 47302 AN: 67974

Other (OTH) AF: 0.731 AC: 1543 AN: 2112

Alfa AF: 0.540 Hom.: 1615

Bravo AF: 0.668

Asia WGS AF: 0.781 AC: 2718 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.4
DANN	Benign	0.83
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: rs10832976; hg19: chr11-18776236;