NM_002412.5:c.-13+292C>T

Variant names:

• chr10-129467588-C-T
• rs12356501
• NM_002412.5:c.-13+292C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002412.5(MGMT):​c.-13+292C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.532 in 259,636 control chromosomes in the GnomAD database, including 40,117 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 0.50 (21488 hom., cov: 33)
  • Exomes 𝑓: 0.58 (18629 hom.)
• Consequence: MGMT NM_002412.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.108
• Publications: 13 publications found

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]

ENSG00000296036 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.614 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002412.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MGMT	NM_002412.5	MANE Select	c.-13+292C>T		intron	N/A	NP_002403.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MGMT	ENST00000651593.1	MANE Select	c.-13+292C>T		intron	N/A	ENSP00000498729.1
	MGMT	ENST00000306010.8	TSL:1	c.81+292C>T		intron	N/A	ENSP00000302111.7
	ENSG00000296036	ENST00000735692.1		n.73G>A		non_coding_transcript_exon	Exon 1 of 4

Frequencies

GnomAD3 genomes AF: 0.500 AC: 76040 AN: 151938 Hom.: 21488 Cov.: 33

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.555

Gnomad AMR AF: 0.563

Gnomad ASJ AF: 0.631

Gnomad EAS AF: 0.633

Gnomad SAS AF: 0.568

Gnomad FIN AF: 0.658

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.609

Gnomad OTH AF: 0.548

GnomAD4 exome AF: 0.576 AC: 62004 AN: 107580 Hom.: 18629 AF XY: 0.574 AC XY: 29469 AN XY: 51310

African (AFR) AF: 0.173 AC: 383 AN: 2212

American (AMR) AF: 0.516 AC: 66 AN: 128

Ashkenazi Jewish (ASJ) AF: 0.577 AC: 374 AN: 648

East Asian (EAS) AF: 0.644 AC: 278 AN: 432

South Asian (SAS) AF: 0.560 AC: 1174 AN: 2098

European-Finnish (FIN) AF: 0.656 AC: 21 AN: 32

Middle Eastern (MID) AF: 0.539 AC: 124 AN: 230

European-Non Finnish (NFE) AF: 0.586 AC: 57495 AN: 98184

Other (OTH) AF: 0.578 AC: 2089 AN: 3616

GnomAD4 genome AF: 0.500 AC: 76050 AN: 152056 Hom.: 21488 Cov.: 33 AF XY: 0.505 AC XY: 37560 AN XY: 74306

African (AFR) AF: 0.218 AC: 9067 AN: 41502

American (AMR) AF: 0.562 AC: 8594 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.631 AC: 2191 AN: 3472

East Asian (EAS) AF: 0.632 AC: 3240 AN: 5124

South Asian (SAS) AF: 0.568 AC: 2736 AN: 4816

European-Finnish (FIN) AF: 0.658 AC: 6974 AN: 10592

Middle Eastern (MID) AF: 0.629 AC: 185 AN: 294

European-Non Finnish (NFE) AF: 0.609 AC: 41397 AN: 67946

Other (OTH) AF: 0.549 AC: 1160 AN: 2114

Alfa AF: 0.569 Hom.: 27733

Bravo AF: 0.483

Asia WGS AF: 0.582 AC: 2025 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.2
DANN	Benign	0.64
PhyloP100		-0.11
PromoterAI		0.015	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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: rs12356501; hg19: chr10-131265852;