chr7-2235542-G-A

Variant names:

• chr7-2235542-G-A
• rs11547272
• NM_013393.3:c.321C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BA1

The NM_013393.3(MRM2):​c.321C>T​(p.Phe107Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00311 in 1,611,642 control chromosomes in the GnomAD database, including 144 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.016 (66 hom., cov: 32)
  • Exomes 𝑓: 0.0018 (78 hom.)
• Consequence: MRM2 NM_013393.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: -1.39
• Publications: 1 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.119).
• BP6: Variant 7-2235542-G-A is Benign according to our data. Variant chr7-2235542-G-A is described in ClinVar as Benign. ClinVar VariationId is 787048.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.39 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.054 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013393.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRM2	NM_013393.3	MANE Select	c.321C>T	p.Phe107Phe	synonymous	Exon 3 of 3	NP_037525.1	Q9UI43

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRM2	ENST00000242257.14	TSL:1 MANE Select	c.321C>T	p.Phe107Phe	synonymous	Exon 3 of 3	ENSP00000242257.8	Q9UI43
	MRM2	ENST00000486040.1	TSL:1	n.*776C>T		non_coding_transcript_exon	Exon 4 of 4	ENSP00000498090.1	A0A3B3ITW8
	ENSG00000286192	ENST00000651235.1		n.*776C>T		non_coding_transcript_exon	Exon 4 of 24	ENSP00000498895.1	A0A3B3ITW8

Frequencies

GnomAD3 genomes AF: 0.0160 AC: 2438 AN: 152184 Hom.: 66 Cov.: 32

Gnomad AFR AF: 0.0559

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00504

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000220

Gnomad OTH AF: 0.0143

GnomAD2 exomes AF: 0.00414 AC: 1033 AN: 249718 AF XY: 0.00295

Gnomad AFR exome AF: 0.0574

Gnomad AMR exome AF: 0.00241

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000545

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000168

Gnomad OTH exome AF: 0.00148

GnomAD4 exome AF: 0.00175 AC: 2561 AN: 1459340 Hom.: 78 Cov.: 31 AF XY: 0.00158 AC XY: 1145 AN XY: 725838

African (AFR) AF: 0.0609 AC: 2036 AN: 33422

American (AMR) AF: 0.00291 AC: 130 AN: 44672

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26112

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39682

South Asian (SAS) AF: 0.000116 AC: 10 AN: 86214

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52546

Middle Eastern (MID) AF: 0.00156 AC: 9 AN: 5766

European-Non Finnish (NFE) AF: 0.000137 AC: 152 AN: 1110624

Other (OTH) AF: 0.00368 AC: 222 AN: 60302

GnomAD4 genome AF: 0.0160 AC: 2444 AN: 152302 Hom.: 66 Cov.: 32 AF XY: 0.0153 AC XY: 1143 AN XY: 74468

African (AFR) AF: 0.0559 AC: 2322 AN: 41560

American (AMR) AF: 0.00503 AC: 77 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000220 AC: 15 AN: 68028

Other (OTH) AF: 0.0142 AC: 30 AN: 2114

Alfa AF: 0.0111 Hom.: 31

Bravo AF: 0.0186

Asia WGS AF: 0.00260 AC: 10 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	MRM2-related disorder (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	5.2
DANN	Benign	0.96
PhyloP100		-1.4
Mutation Taster		=99/1	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: rs11547272; hg19: chr7-2275177; COSMIC: COSV54249117; COSMIC: COSV54249117;