rs1856679

Positions:

• chr10-46998036-A-G

Variant summary

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

The NM_001042357.5(PTPN20):​c.1135-1876A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.492 in 151,946 control chromosomes in the GnomAD database, including 19,636 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 0.49 (19636 hom., cov: 32)
• Consequence: PTPN20 NM_001042357.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.190

Genes affected

PTPN20 (HGNC:23423): (protein tyrosine phosphatase non-receptor type 20) The product of this gene belongs to the family of classical tyrosine-specific protein tyrosine phosphatases. Many protein tyrosine phosphatases have been shown to regulate fundamental cellular processes. The encoded protein appears to be targeted to sites of actin polymerization. A pseudogene of this gene has been defined on chromosome 10. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.676 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPN20	NM_001042357.5	c.1135-1876A>G		intron_variant		ENST00000374339.5	NP_001035816.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPN20	ENST00000374339.5	c.1135-1876A>G		intron_variant		1	NM_001042357.5	ENSP00000363459	P2

Frequencies

GnomAD3 genomes AF: 0.492 AC: 74669 AN: 151828 Hom.: 19604 Cov.: 32

Gnomad AFR AF: 0.683

Gnomad AMI AF: 0.444

Gnomad AMR AF: 0.385

Gnomad ASJ AF: 0.444

Gnomad EAS AF: 0.503

Gnomad SAS AF: 0.553

Gnomad FIN AF: 0.408

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.410

Gnomad OTH AF: 0.499

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

GnomAD4 genome AF: 0.492 AC: 74752 AN: 151946 Hom.: 19636 Cov.: 32 AF XY: 0.490 AC XY: 36373 AN XY: 74284

Gnomad4 AFR AF: 0.683

Gnomad4 AMR AF: 0.385

Gnomad4 ASJ AF: 0.444

Gnomad4 EAS AF: 0.503

Gnomad4 SAS AF: 0.553

Gnomad4 FIN AF: 0.408

Gnomad4 NFE AF: 0.410

Gnomad4 OTH AF: 0.502

Alfa AF: 0.476 Hom.: 1679

Bravo AF: 0.499

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.3
DANN	Benign	0.39

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1856679; hg19: chr10-48741326;