12-112418839-G-A

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000531326.1(PTPN11):n.331G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0952 in 498,058 control chromosomes in the GnomAD database, including 2,695 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 957 hom., cov: 33)

Exomes 𝑓: 0.091 ( 1738 hom. )

Consequence

PTPN11
ENST00000531326.1 non_coding_transcript_exon

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.486

Variant links:

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]

PTPN11 links:

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]

RPL6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.64).

BP6

Variant 12-112418839-G-A is Benign according to our data. Variant chr12-112418839-G-A is described in ClinVar as [Benign]. Clinvar id is 307220.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.223 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Protein	UniProt
RPL6	NM_001320141.2 link	c.-340C>T	upstream_gene_variant	NP_001307070.1	Q02878A0A024RBK3
RPL6	XM_047429302.1 link	c.-442C>T	upstream_gene_variant	XP_047285258.1
RPL6	XM_047429303.1 link	c.-336C>T	upstream_gene_variant	XP_047285259.1
RPL6	XM_047429304.1 link	c.-436C>T	upstream_gene_variant	XP_047285260.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPN11	ENST00000531326.1 link	n.331G>A		non_coding_transcript_exon_variant	Exon 2 of 2	4
RPL6	ENST00000551291.6 link	c.-340C>T		upstream_gene_variant		3		ENSP00000448067.2		F8VU16

Frequencies

GnomAD3 genomes

AF:

0.104

AC:

15782

AN:

152154

Hom.:

956

Cov.:

show subpopulations

Gnomad AFR

AF:

0.149

Gnomad AMI

AF:

0.0186

Gnomad AMR

AF:

0.0640

Gnomad ASJ

AF:

0.0297

Gnomad EAS

AF:

0.234

Gnomad SAS

AF:

0.130

Gnomad FIN

AF:

0.101

Gnomad MID

AF:

0.106

Gnomad NFE

AF:

0.0794

Gnomad OTH

AF:

0.0870

GnomAD4 exome

AF:

0.0915

AC:

31628

AN:

345786

Hom.:

1738

Cov.:

AF XY:

0.0924

AC XY:

16883

AN XY:

182722

show subpopulations

Gnomad4 AFR exome

AF:

0.142

Gnomad4 AMR exome

AF:

0.0582

Gnomad4 ASJ exome

AF:

0.0353

Gnomad4 EAS exome

AF:

0.173

Gnomad4 SAS exome

AF:

0.127

Gnomad4 FIN exome

AF:

0.109

Gnomad4 NFE exome

AF:

0.0775

Gnomad4 OTH exome

AF:

0.0925

GnomAD4 genome

AF:

0.104

AC:

15795

AN:

152272

Hom.:

957

Cov.:

AF XY:

0.104

AC XY:

7778

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.149

Gnomad4 AMR

AF:

0.0639

Gnomad4 ASJ

AF:

0.0297

Gnomad4 EAS

AF:

0.234

Gnomad4 SAS

AF:

0.130

Gnomad4 FIN

AF:

0.101

Gnomad4 NFE

AF:

0.0794

Gnomad4 OTH

AF:

0.0856

Alfa

AF:

0.0409

Hom.:

Bravo

AF:

0.104

Asia WGS

AF:

0.214

AC:

743

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 19, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Noonan syndrome 1

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

LEOPARD syndrome 1

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Metachondromatosis

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Juvenile myelomonocytic leukemia;C0410530:Metachondromatosis;C4551484:LEOPARD syndrome 1;C4551602:Noonan syndrome 1

Benign:1

Oct 31, 2021

Fulgent Genetics, Fulgent Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

RASopathy

Benign:1

Jan 20, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

6.9

DANN

Benign

0.93

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over