NM_002834.5:c.-161T>A

Variant names:

• chr12-112418951-T-A
• rs893158717
• NM_002834.5:c.-161T>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_002834.5(PTPN11):​c.-161T>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000287 in 696,190 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000029 (0 hom.)
• Consequence: PTPN11 NM_002834.5 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:3
• Conservation: PhyloP100: 0.988
• Publications: 0 publications found

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]

RPL6 (HGNC:10362): (ribosomal protein L6) This gene encodes a protein component of the 60S ribosomal subunit. This protein can bind specifically to domain C of the tax-responsive enhancer element of human T-cell leukemia virus type 1, and may participate in tax-mediated transactivation of transcription. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed throughout the genome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BS2: High AC in GnomAdExome4 at 20 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002834.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPN11	NM_002834.5	MANE Select	c.-161T>A		5_prime_UTR	Exon 1 of 16	NP_002825.3
	PTPN11	NM_001330437.2		c.-161T>A		5_prime_UTR	Exon 1 of 16	NP_001317366.1	Q06124-1
	PTPN11	NM_001374625.1		c.-161T>A		5_prime_UTR	Exon 1 of 16	NP_001361554.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPN11	ENST00000351677.7	TSL:1 MANE Select	c.-161T>A		5_prime_UTR	Exon 1 of 16	ENSP00000340944.3	Q06124-2
	PTPN11	ENST00000392597.5	TSL:1	c.-161T>A		5_prime_UTR	Exon 1 of 11	ENSP00000376376.1	Q06124-3
	PTPN11	ENST00000690210.1		c.-161T>A		5_prime_UTR	Exon 1 of 17	ENSP00000509272.1	A0A8I5KW48

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.0000287 AC: 20 AN: 696190 Hom.: 0 Cov.: 9 AF XY: 0.0000355 AC XY: 13 AN XY: 365726

African (AFR) AF: 0.00 AC: 0 AN: 14852

American (AMR) AF: 0.00 AC: 0 AN: 30858

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19684

East Asian (EAS) AF: 0.000719 AC: 20 AN: 27804

South Asian (SAS) AF: 0.00 AC: 0 AN: 62320

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32742

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2706

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 470692

Other (OTH) AF: 0.00 AC: 0 AN: 34532

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

Asia WGS AF: 0.000289 AC: 1 AN: 3468

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	LEOPARD syndrome 1 (1)
-	1	-	Metachondromatosis (1)
-	1	-	Noonan syndrome 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	19
DANN	Benign	0.94
PhyloP100		0.99
PromoterAI		0.016	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

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: rs893158717; hg19: chr12-112856755;