rs10764899

Positions:

• chr10-129698898-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_002412.5(MGMT):​c.126-8997C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.654 in 152,136 control chromosomes in the GnomAD database, including 34,628 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 0.65 (34628 hom., cov: 34)
• Consequence: MGMT NM_002412.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.23

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.23).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.773 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MGMT	NM_002412.5	c.126-8997C>T		intron_variant		ENST00000651593.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MGMT	ENST00000651593.1	c.126-8997C>T		intron_variant			NM_002412.5	P1
MGMT	ENST00000306010.8	c.219-8997C>T		intron_variant		1
	ENST00000598332.2	n.304+1981G>A		intron_variant, non_coding_transcript_variant		5
	ENST00000628250.1	n.300+1981G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.655 AC: 99527 AN: 152018 Hom.: 34632 Cov.: 34

Gnomad AFR AF: 0.401

Gnomad AMI AF: 0.630

Gnomad AMR AF: 0.677

Gnomad ASJ AF: 0.746

Gnomad EAS AF: 0.638

Gnomad SAS AF: 0.765

Gnomad FIN AF: 0.738

Gnomad MID AF: 0.772

Gnomad NFE AF: 0.779

Gnomad OTH AF: 0.669

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.654 AC: 99541 AN: 152136 Hom.: 34628 Cov.: 34 AF XY: 0.654 AC XY: 48676 AN XY: 74376

Gnomad4 AFR AF: 0.401

Gnomad4 AMR AF: 0.677

Gnomad4 ASJ AF: 0.746

Gnomad4 EAS AF: 0.638

Gnomad4 SAS AF: 0.765

Gnomad4 FIN AF: 0.738

Gnomad4 NFE AF: 0.779

Gnomad4 OTH AF: 0.670

Alfa AF: 0.699 Hom.: 5667

Bravo AF: 0.631

Asia WGS AF: 0.667 AC: 2318 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.23
CADD	Benign	19
DANN	Benign	0.74

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

Other links and lift over

dbSNP: rs10764899; hg19: chr10-131497162;