7-2238591-C-T

Variant names:

• chr7-2238591-C-T
• rs7799006
• ENST00000486040.1:n.*177G>A

Variant summary

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

The ENST00000486040.1(MRM2):​n.*177G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 151,980 control chromosomes in the GnomAD database, including 8,813 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 0.34 (8808 hom., cov: 31)
  • Exomes 𝑓: 0.40 (5 hom.)
• Consequence: MRM2 ENST00000486040.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.183
• Publications: 36 publications found

Genes affected

MRM2 (HGNC:16352): (mitochondrial rRNA methyltransferase 2) The protein encoded by this gene is a member of the S-adenosylmethionine-binding protein family. It is a nucleolar protein and it may be involved in the processing and modification of rRNA. This gene has been suggested to be involved in cell cycle control and DNA repair. [provided by RefSeq, Jul 2008]

MRM2 Gene-Disease associations (from GenCC):

• mitochondrial DNA depletion syndrome 17

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000286192 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.496 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRM2	NM_013393.3	c.298+827G>A		intron_variant	Intron 2 of 2	ENST00000242257.14	NP_037525.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000286192	ENST00000651235.1	n.*177G>A		non_coding_transcript_exon_variant	Exon 3 of 24			ENSP00000498895.1
ENSG00000286192	ENST00000651235.1	n.*177G>A		3_prime_UTR_variant	Exon 3 of 24			ENSP00000498895.1
MRM2	ENST00000242257.14	c.298+827G>A		intron_variant	Intron 2 of 2	1	NM_013393.3	ENSP00000242257.8

Frequencies

GnomAD3 genomes AF: 0.335 AC: 50918 AN: 151784 Hom.: 8805 Cov.: 31

Gnomad AFR AF: 0.290

Gnomad AMI AF: 0.222

Gnomad AMR AF: 0.377

Gnomad ASJ AF: 0.257

Gnomad EAS AF: 0.512

Gnomad SAS AF: 0.327

Gnomad FIN AF: 0.276

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.356

Gnomad OTH AF: 0.347

GnomAD4 exome AF: 0.397 AC: 31 AN: 78 Hom.: 5 Cov.: 0 AF XY: 0.446 AC XY: 25 AN XY: 56

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.250 AC: 1 AN: 4

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.333 AC: 2 AN: 6

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.424 AC: 28 AN: 66

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome AF: 0.335 AC: 50934 AN: 151902 Hom.: 8808 Cov.: 31 AF XY: 0.335 AC XY: 24839 AN XY: 74214

African (AFR) AF: 0.290 AC: 12008 AN: 41424

American (AMR) AF: 0.377 AC: 5752 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.257 AC: 890 AN: 3462

East Asian (EAS) AF: 0.512 AC: 2643 AN: 5158

South Asian (SAS) AF: 0.327 AC: 1572 AN: 4810

European-Finnish (FIN) AF: 0.276 AC: 2912 AN: 10534

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.356 AC: 24177 AN: 67932

Other (OTH) AF: 0.345 AC: 729 AN: 2112

Alfa AF: 0.351 Hom.: 38080

Bravo AF: 0.344

Asia WGS AF: 0.433 AC: 1504 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.0
DANN	Benign	0.70
PhyloP100		0.18
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: rs7799006; hg19: chr7-2278226;