chr12-6960457-T-C

Position:

• chr12-6960457-T-C

Variant summary

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

The NM_002831.6(PTPN6):​c.1673+22T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.861 in 1,606,846 control chromosomes in the GnomAD database, including 599,355 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 0.79 (48561 hom., cov: 33)
  • Exomes 𝑓: 0.87 (550794 hom.)
• Consequence: PTPN6 NM_002831.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.42

Genes affected

PTPN6 (HGNC:9658): (protein tyrosine phosphatase non-receptor type 6) The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. N-terminal part of this PTP contains two tandem Src homolog (SH2) domains, which act as protein phospho-tyrosine binding domains, and mediate the interaction of this PTP with its substrates. This PTP is expressed primarily in hematopoietic cells, and functions as an important regulator of multiple signaling pathways in hematopoietic cells. This PTP has been shown to interact with, and dephosphorylate a wide spectrum of phospho-proteins involved in hematopoietic cell signaling. Multiple alternatively spliced variants of this gene, which encode distinct isoforms, have been reported. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.868 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTPN6	NM_002831.6	c.1673+22T>C		intron_variant		ENST00000318974.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPN6	ENST00000318974.14	c.1673+22T>C		intron_variant		1	NM_002831.6	P1

Frequencies

GnomAD3 genomes AF: 0.787 AC: 119636 AN: 152022 Hom.: 48551 Cov.: 33

Gnomad AFR AF: 0.565

Gnomad AMI AF: 0.872

Gnomad AMR AF: 0.856

Gnomad ASJ AF: 0.907

Gnomad EAS AF: 0.856

Gnomad SAS AF: 0.887

Gnomad FIN AF: 0.867

Gnomad MID AF: 0.829

Gnomad NFE AF: 0.874

Gnomad OTH AF: 0.813

GnomAD3 exomes AF: 0.858 AC: 211313 AN: 246382 Hom.: 91430 AF XY: 0.863 AC XY: 115711 AN XY: 134082

Gnomad AFR exome AF: 0.555

Gnomad AMR exome AF: 0.883

Gnomad ASJ exome AF: 0.902

Gnomad EAS exome AF: 0.856

Gnomad SAS exome AF: 0.884

Gnomad FIN exome AF: 0.862

Gnomad NFE exome AF: 0.879

Gnomad OTH exome AF: 0.858

GnomAD4 exome AF: 0.868 AC: 1263368 AN: 1454706 Hom.: 550794 Cov.: 38 AF XY: 0.870 AC XY: 629833 AN XY: 724046

Gnomad4 AFR exome AF: 0.550

Gnomad4 AMR exome AF: 0.878

Gnomad4 ASJ exome AF: 0.904

Gnomad4 EAS exome AF: 0.818

Gnomad4 SAS exome AF: 0.884

Gnomad4 FIN exome AF: 0.859

Gnomad4 NFE exome AF: 0.879

Gnomad4 OTH exome AF: 0.848

GnomAD4 genome AF: 0.787 AC: 119683 AN: 152140 Hom.: 48561 Cov.: 33 AF XY: 0.790 AC XY: 58778 AN XY: 74370

Gnomad4 AFR AF: 0.564

Gnomad4 AMR AF: 0.856

Gnomad4 ASJ AF: 0.907

Gnomad4 EAS AF: 0.855

Gnomad4 SAS AF: 0.887

Gnomad4 FIN AF: 0.867

Gnomad4 NFE AF: 0.874

Gnomad4 OTH AF: 0.816

Alfa AF: 0.866 Hom.: 35902

Bravo AF: 0.774

Asia WGS AF: 0.833 AC: 2894 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.84
DANN	Benign	0.60
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs759052; hg19: chr12-7069620;