12-112468611-A-G

Position:

• chr12-112468611-A-G

Variant summary

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

The ENST00000351677.7(PTPN11):​c.757-4333A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.707 in 152,122 control chromosomes in the GnomAD database, including 40,543 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 0.71 (40543 hom., cov: 31)
• Consequence: PTPN11 ENST00000351677.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.127

Genes affected

PTPN11 (HGNC:9644): (protein tyrosine phosphatase non-receptor type 11) 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. This PTP contains two tandem Src homology-2 domains, which function as phospho-tyrosine binding domains and mediate the interaction of this PTP with its substrates. This PTP is widely expressed in most tissues and plays a regulatory role in various cell signaling events that are important for a diversity of cell functions, such as mitogenic activation, metabolic control, transcription regulation, and cell migration. Mutations in this gene are a cause of Noonan syndrome as well as acute myeloid leukemia. [provided by RefSeq, Aug 2016]

LOC124903023 (HGNC:):

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 (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPN11	NM_002834.5	c.757-4333A>G		intron_variant		ENST00000351677.7	NP_002825.3
LOC124903023	XR_007063466.1	n.222+29T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPN11	ENST00000351677.7	c.757-4333A>G		intron_variant		1	NM_002834.5	ENSP00000340944	A1

Frequencies

GnomAD3 genomes AF: 0.707 AC: 107457 AN: 152004 Hom.: 40469 Cov.: 31

Gnomad AFR AF: 0.928

Gnomad AMI AF: 0.603

Gnomad AMR AF: 0.739

Gnomad ASJ AF: 0.349

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.919

Gnomad FIN AF: 0.600

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.566

Gnomad OTH AF: 0.678

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

GnomAD4 genome AF: 0.707 AC: 107594 AN: 152122 Hom.: 40543 Cov.: 31 AF XY: 0.716 AC XY: 53228 AN XY: 74382

Gnomad4 AFR AF: 0.928

Gnomad4 AMR AF: 0.739

Gnomad4 ASJ AF: 0.349

Gnomad4 EAS AF: 0.998

Gnomad4 SAS AF: 0.919

Gnomad4 FIN AF: 0.600

Gnomad4 NFE AF: 0.566

Gnomad4 OTH AF: 0.681

Alfa AF: 0.588 Hom.: 38001

Bravo AF: 0.722

Asia WGS AF: 0.945 AC: 3287 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	5.5
DANN	Benign	0.66

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: rs11066320; hg19: chr12-112906415;