12-6947971-A-T

Position:

• chr12-6947971-A-T

Variant summary

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

The NM_080548.5(PTPN6):​c.14+1232A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.595 in 151,912 control chromosomes in the GnomAD database, including 28,190 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 0.60 (28190 hom., cov: 30)
• Consequence: PTPN6 NM_080548.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.690

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]

PTPN6 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.788 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPN6	NM_080548.5	c.14+1232A>T		intron_variant			NP_536858.1
PTPN6	XM_011520988.2	c.14+1232A>T		intron_variant			XP_011519290.1
PTPN6	XM_047429231.1	c.14+1232A>T		intron_variant			XP_047285187.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPN6	ENST00000399448.5	c.14+1232A>T		intron_variant		1		ENSP00000382376.1
PTPN6	ENST00000543115.5	c.14+1232A>T		intron_variant		4		ENSP00000443393.1
PTPN6	ENST00000534900.5	n.130+1232A>T		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.595 AC: 90285 AN: 151794 Hom.: 28135 Cov.: 30

Gnomad AFR AF: 0.795

Gnomad AMI AF: 0.496

Gnomad AMR AF: 0.609

Gnomad ASJ AF: 0.415

Gnomad EAS AF: 0.525

Gnomad SAS AF: 0.658

Gnomad FIN AF: 0.490

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.498

Gnomad OTH AF: 0.570

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

GnomAD4 genome AF: 0.595 AC: 90397 AN: 151912 Hom.: 28190 Cov.: 30 AF XY: 0.594 AC XY: 44098 AN XY: 74216

Gnomad4 AFR AF: 0.795

Gnomad4 AMR AF: 0.609

Gnomad4 ASJ AF: 0.415

Gnomad4 EAS AF: 0.524

Gnomad4 SAS AF: 0.659

Gnomad4 FIN AF: 0.490

Gnomad4 NFE AF: 0.498

Gnomad4 OTH AF: 0.569

Alfa AF: 0.389 Hom.: 945

Bravo AF: 0.611

Asia WGS AF: 0.658 AC: 2286 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.67
DANN	Benign	0.77

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: rs7310161; hg19: chr12-7057134;