chr11-18771813-T-C

Variant names:

• chr11-18771813-T-C
• rs4075664
• NM_006906.2:c.20+126A>G

Variant summary

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

The NM_006906.2(PTPN5):​c.20+126A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.497 in 791,040 control chromosomes in the GnomAD database, including 101,769 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 0.46 (17086 hom., cov: 33)
  • Exomes 𝑓: 0.51 (84683 hom.)
• Consequence: PTPN5 NM_006906.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.346
• Publications: 7 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.851 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPN5	NM_006906.2	c.20+126A>G		intron_variant	Intron 2 of 14	ENST00000358540.7	NP_008837.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPN5	ENST00000358540.7	c.20+126A>G		intron_variant	Intron 2 of 14	1	NM_006906.2	ENSP00000351342.2
PTPN5	ENST00000396168.1	c.-52-5930A>G		intron_variant	Intron 1 of 13	1		ENSP00000379471.1
PTPN5	ENST00000396170.5	c.20+126A>G		intron_variant	Intron 2 of 14	2		ENSP00000379473.1

Frequencies

GnomAD3 genomes AF: 0.458 AC: 69606 AN: 151948 Hom.: 17076 Cov.: 33

Gnomad AFR AF: 0.306

Gnomad AMI AF: 0.473

Gnomad AMR AF: 0.554

Gnomad ASJ AF: 0.397

Gnomad EAS AF: 0.874

Gnomad SAS AF: 0.581

Gnomad FIN AF: 0.513

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.483

Gnomad OTH AF: 0.465

GnomAD4 exome AF: 0.506 AC: 323478 AN: 638974 Hom.: 84683 AF XY: 0.505 AC XY: 173411 AN XY: 343310

African (AFR) AF: 0.305 AC: 4272 AN: 13988

American (AMR) AF: 0.603 AC: 15144 AN: 25096

Ashkenazi Jewish (ASJ) AF: 0.394 AC: 7350 AN: 18650

East Asian (EAS) AF: 0.873 AC: 26675 AN: 30566

South Asian (SAS) AF: 0.536 AC: 29788 AN: 55616

European-Finnish (FIN) AF: 0.504 AC: 25823 AN: 51230

Middle Eastern (MID) AF: 0.428 AC: 1251 AN: 2920

European-Non Finnish (NFE) AF: 0.483 AC: 197131 AN: 408182

Other (OTH) AF: 0.490 AC: 16044 AN: 32726

GnomAD4 genome AF: 0.458 AC: 69657 AN: 152066 Hom.: 17086 Cov.: 33 AF XY: 0.466 AC XY: 34656 AN XY: 74348

African (AFR) AF: 0.307 AC: 12710 AN: 41462

American (AMR) AF: 0.555 AC: 8483 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.397 AC: 1379 AN: 3470

East Asian (EAS) AF: 0.873 AC: 4519 AN: 5178

South Asian (SAS) AF: 0.581 AC: 2800 AN: 4818

European-Finnish (FIN) AF: 0.513 AC: 5418 AN: 10560

Middle Eastern (MID) AF: 0.480 AC: 141 AN: 294

European-Non Finnish (NFE) AF: 0.483 AC: 32797 AN: 67972

Other (OTH) AF: 0.465 AC: 980 AN: 2108

Alfa AF: 0.477 Hom.: 17268

Bravo AF: 0.455

Asia WGS AF: 0.687 AC: 2387 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.63
DANN	Benign	0.55
PhyloP100		-0.35
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: rs4075664; hg19: chr11-18793360;