Variant 10-129766906-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_002412.5(MGMT):c.533A>G(p.Lys178Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 1,613,358 control chromosomes in the GnomAD database, including 12,337 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.087 ( 826 hom., cov: 34)

Exomes 𝑓: 0.12 ( 11511 hom. )

Consequence

MGMT
NM_002412.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.18

Variant links:

Genes affected

MGMT (HGNC:7059): (O-6-methylguanine-DNA methyltransferase) Alkylating agents are potent carcinogens that can result in cell death, mutation and cancer. The protein encoded by this gene is a DNA repair protein that is involved in cellular defense against mutagenesis and toxicity from alkylating agents. The protein catalyzes transfer of methyl groups from O(6)-alkylguanine and other methylated moieties of the DNA to its own molecule, which repairs the toxic lesions. Methylation of the genes promoter has been associated with several cancer types, including colorectal cancer, lung cancer, lymphoma and glioblastoma. [provided by RefSeq, Sep 2015]

MGMT links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0015718937).

BP6

Variant 10-129766906-A-G is Benign according to our data. Variant chr10-129766906-A-G is described in ClinVar as [Benign]. Clinvar id is 1230786.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.127 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MGMT	NM_002412.5 linkuse as main transcript	c.533A>G	p.Lys178Arg	missense_variant	5/5	ENST00000651593.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MGMT	ENST00000651593.1 linkuse as main transcript	c.533A>G	p.Lys178Arg	missense_variant	5/5		NM_002412.5	P1
MGMT	ENST00000306010.8 linkuse as main transcript	c.626A>G	p.Lys209Arg	missense_variant	5/5	1

Frequencies

GnomAD3 genomes

AF:

0.0872

AC:

13274

AN:

152220

Hom.:

827

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0225

Gnomad AMI

AF:

0.195

Gnomad AMR

AF:

0.0719

Gnomad ASJ

AF:

0.0764

Gnomad EAS

AF:

0.0118

Gnomad SAS

AF:

0.0752

Gnomad FIN

AF:

0.130

Gnomad MID

AF:

0.127

Gnomad NFE

AF:

0.129

Gnomad OTH

AF:

0.0865

GnomAD3 exomes

AF:

0.0937

AC:

23396

AN:

249700

Hom.:

1374

AF XY:

0.0979

AC XY:

13258

AN XY:

135388

show subpopulations

Gnomad AFR exome

AF:

0.0190

Gnomad AMR exome

AF:

0.0474

Gnomad ASJ exome

AF:

0.0882

Gnomad EAS exome

AF:

0.00887

Gnomad SAS exome

AF:

0.0810

Gnomad FIN exome

AF:

0.123

Gnomad NFE exome

AF:

0.130

Gnomad OTH exome

AF:

0.0984

GnomAD4 exome

AF:

0.120

AC:

174969

AN:

1461020

Hom.:

11511

Cov.:

AF XY:

0.119

AC XY:

86680

AN XY:

726818

show subpopulations

Gnomad4 AFR exome

AF:

0.0180

Gnomad4 AMR exome

AF:

0.0494

Gnomad4 ASJ exome

AF:

0.0884

Gnomad4 EAS exome

AF:

0.00496

Gnomad4 SAS exome

AF:

0.0831

Gnomad4 FIN exome

AF:

0.121

Gnomad4 NFE exome

AF:

0.134

Gnomad4 OTH exome

AF:

0.106

GnomAD4 genome

AF:

0.0871

AC:

13270

AN:

152338

Hom.:

826

Cov.:

AF XY:

0.0857

AC XY:

6387

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.0224

Gnomad4 AMR

AF:

0.0717

Gnomad4 ASJ

AF:

0.0764

Gnomad4 EAS

AF:

0.0116

Gnomad4 SAS

AF:

0.0758

Gnomad4 FIN

AF:

0.130

Gnomad4 NFE

AF:

0.129

Gnomad4 OTH

AF:

0.0866

Alfa

AF:

0.117

Hom.:

2412

Bravo

AF:

0.0799

TwinsUK

AF:

0.143

AC:

532

ALSPAC

AF:

0.129

AC:

498

ESP6500AA

AF:

0.0222

AC:

ESP6500EA

AF:

0.128

AC:

1105

ExAC

AF:

0.0932

AC:

11306

Asia WGS

AF:

0.0380

AC:

133

AN:

3478

EpiCase

AF:

0.133

EpiControl

AF:

0.128

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 07, 2019

This variant is associated with the following publications: (PMID: 17234722, 18812520) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.75

Cadd

Benign

8.9

Dann

Benign

0.95

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.085

LIST_S2

Benign

0.45

MetaRNN

Benign

0.0016

MetaSVM

Benign

-0.95

MutationTaster

Benign

1.0

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.92

REVEL

Benign

0.073

Sift

Benign

0.046

Sift4G

Benign

0.12

Vest4

0.057

MPC

0.043

ClinPred

0.0094

GERP RS

-3.6

gMVP

0.31

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

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