Variant 10-129707928-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_002412.5(MGMT):c.159C>T(p.Leu53=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 1,612,080 control chromosomes in the GnomAD database, including 12,582 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 0.13 ( 1547 hom., cov: 32)

Exomes 𝑓: 0.12 ( 11035 hom. )

Consequence

MGMT
NM_002412.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.314

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP7

Synonymous conserved (PhyloP=-0.314 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.186 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MGMT	NM_002412.5 linkuse as main transcript	c.159C>T	p.Leu53=	synonymous_variant	3/5	ENST00000651593.1	NP_002403.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
MGMT	ENST00000651593.1 linkuse as main transcript	c.159C>T	p.Leu53=	synonymous_variant	3/5		NM_002412.5	ENSP00000498729	P1
MGMT	ENST00000306010.8 linkuse as main transcript	c.252C>T	p.Leu84=	synonymous_variant	3/5	1		ENSP00000302111
MGMT	ENST00000462672.1 linkuse as main transcript	n.320C>T		non_coding_transcript_exon_variant	2/4	3

Frequencies

GnomAD3 genomes

AF:

0.134

AC:

20336

AN:

151906

Hom.:

1534

Cov.:

show subpopulations

Gnomad AFR

AF:

0.172

Gnomad AMI

AF:

0.0625

Gnomad AMR

AF:

0.191

Gnomad ASJ

AF:

0.118

Gnomad EAS

AF:

0.106

Gnomad SAS

AF:

0.136

Gnomad FIN

AF:

0.0395

Gnomad MID

AF:

0.117

Gnomad NFE

AF:

0.116

Gnomad OTH

AF:

0.142

GnomAD3 exomes

AF:

0.133

AC:

33222

AN:

250436

Hom.:

2583

AF XY:

0.129

AC XY:

17488

AN XY:

135434

show subpopulations

Gnomad AFR exome

AF:

0.173

Gnomad AMR exome

AF:

0.228

Gnomad ASJ exome

AF:

0.134

Gnomad EAS exome

AF:

0.0956

Gnomad SAS exome

AF:

0.141

Gnomad FIN exome

AF:

0.0460

Gnomad NFE exome

AF:

0.117

Gnomad OTH exome

AF:

0.129

GnomAD4 exome

AF:

0.118

AC:

172611

AN:

1460056

Hom.:

11035

Cov.:

AF XY:

0.119

AC XY:

86105

AN XY:

726336

show subpopulations

Gnomad4 AFR exome

AF:

0.182

Gnomad4 AMR exome

AF:

0.221

Gnomad4 ASJ exome

AF:

0.133

Gnomad4 EAS exome

AF:

0.125

Gnomad4 SAS exome

AF:

0.139

Gnomad4 FIN exome

AF:

0.0475

Gnomad4 NFE exome

AF:

0.113

Gnomad4 OTH exome

AF:

0.125

GnomAD4 genome

AF:

0.134

AC:

20380

AN:

152024

Hom.:

1547

Cov.:

AF XY:

0.133

AC XY:

9873

AN XY:

74302

show subpopulations

Gnomad4 AFR

AF:

0.172

Gnomad4 AMR

AF:

0.192

Gnomad4 ASJ

AF:

0.118

Gnomad4 EAS

AF:

0.106

Gnomad4 SAS

AF:

0.136

Gnomad4 FIN

AF:

0.0395

Gnomad4 NFE

AF:

0.116

Gnomad4 OTH

AF:

0.142

Alfa

AF:

0.126

Hom.:

1730

Bravo

AF:

0.145

Asia WGS

AF:

0.113

AC:

393

AN:

3478

EpiCase

AF:

0.124

EpiControl

AF:

0.120

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

7.1

DANN

Benign

0.59

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over