7-2235542-G-C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_013393.3(MRM2):​c.321C>G​(p.Phe107Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. F107F) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MRM2 NM_013393.3 missense
• Clinical Significance: Not reported in ClinVar
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18799886).

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>G	p.Phe107Leu	missense	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>G	p.Phe107Leu	missense	Exon 3 of 3	ENSP00000242257.8	Q9UI43
	MRM2	ENST00000486040.1	TSL:1	n.*776C>G		non_coding_transcript_exon	Exon 4 of 4	ENSP00000498090.1	A0A3B3ITW8
	ENSG00000286192	ENST00000651235.1		n.*776C>G		non_coding_transcript_exon	Exon 4 of 24	ENSP00000498895.1	A0A3B3ITW8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.90
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	3.6
DANN	Benign	0.90
DEOGEN2	Benign	0.054	T
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.19	N
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.0087	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.97	T
PhyloP100		-1.4
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.14
Sift	Benign	0.68	T
Sift4G	Benign	0.76	T
Polyphen		0.0090	B
Vest4		0.43
MutPred		0.51		Gain of glycosylation at S103 (P = 0.0809)
MVP		0.21
MPC		0.23
ClinPred		0.21	T
GERP RS		-5.2
Varity_R		0.25
gMVP		0.52
Mutation Taster		=67/33	polymorphism

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;