Variant chr10-129467281-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The ENST00000306010.8(MGMT):c.66C>T(p.Arg22=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0635 in 1,543,640 control chromosomes in the GnomAD database, including 3,472 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

Frequency

Genomes: 𝑓 0.050 ( 298 hom., cov: 33)

Exomes 𝑓: 0.065 ( 3174 hom. )

Consequence

MGMT
ENST00000306010.8 synonymous

Scores

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: 0.412

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 -8 ACMG points.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0729 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.-28C>T		5_prime_UTR_variant	1/5	ENST00000651593.1	NP_002403.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
MGMT	ENST00000306010.8 linkuse as main transcript	c.66C>T	p.Arg22=	synonymous_variant	1/5	1		ENSP00000302111
MGMT	ENST00000651593.1 linkuse as main transcript	c.-28C>T		5_prime_UTR_variant	1/5		NM_002412.5	ENSP00000498729	P1
MGMT	ENST00000482547.1 linkuse as main transcript	n.20C>T		non_coding_transcript_exon_variant	1/2	2
MGMT	ENST00000482653.1 linkuse as main transcript	n.53C>T		non_coding_transcript_exon_variant	1/3	3

Frequencies

GnomAD3 genomes

AF:

0.0503

AC:

7658

AN:

152154

Hom.:

298

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0109

Gnomad AMI

AF:

0.147

Gnomad AMR

AF:

0.0369

Gnomad ASJ

AF:

0.0703

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0366

Gnomad FIN

AF:

0.0870

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.0746

Gnomad OTH

AF:

0.0378

GnomAD3 exomes

AF:

0.0555

AC:

8097

AN:

145974

Hom.:

305

AF XY:

0.0564

AC XY:

4450

AN XY:

78894

show subpopulations

Gnomad AFR exome

AF:

0.00904

Gnomad AMR exome

AF:

0.0320

Gnomad ASJ exome

AF:

0.0714

Gnomad EAS exome

AF:

0.000104

Gnomad SAS exome

AF:

0.0419

Gnomad FIN exome

AF:

0.0851

Gnomad NFE exome

AF:

0.0740

Gnomad OTH exome

AF:

0.0643

GnomAD4 exome

AF:

0.0650

AC:

90419

AN:

1391368

Hom.:

3174

Cov.:

AF XY:

0.0649

AC XY:

44581

AN XY:

686666

show subpopulations

Gnomad4 AFR exome

AF:

0.00972

Gnomad4 AMR exome

AF:

0.0340

Gnomad4 ASJ exome

AF:

0.0733

Gnomad4 EAS exome

AF:

0.000145

Gnomad4 SAS exome

AF:

0.0419

Gnomad4 FIN exome

AF:

0.0895

Gnomad4 NFE exome

AF:

0.0706

Gnomad4 OTH exome

AF:

0.0561

GnomAD4 genome

AF:

0.0503

AC:

7660

AN:

152272

Hom.:

298

Cov.:

AF XY:

0.0509

AC XY:

3790

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.0108

Gnomad4 AMR

AF:

0.0370

Gnomad4 ASJ

AF:

0.0703

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.0370

Gnomad4 FIN

AF:

0.0870

Gnomad4 NFE

AF:

0.0746

Gnomad4 OTH

AF:

0.0374

Alfa

AF:

0.0634

Hom.:

154

Bravo

AF:

0.0444

Asia WGS

AF:

0.0190

AC:

AN:

3478

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

LINK: link

Submissions by phenotype

Glioblastoma

Other:1

not provided, no classification provided

literature only

Database of Curated Mutations (DoCM)

Mar 10, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.96

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.79

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.79

Position offset: -6

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