17-36602324-G-C

Variant names:

• chr17-36602324-G-C
• rs545927735
• NM_024864.5:c.514G>C

Variant summary

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

The NM_024864.5(MRM1):​c.514G>C​(p.Asp172His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000888 in 1,576,064 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000042 (0 hom.)
• Consequence: MRM1 NM_024864.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.80
• Publications: 0 publications found

Genes affected

MRM1 (HGNC:26202): (mitochondrial rRNA methyltransferase 1) Enables rRNA (guanosine-2'-O-)-methyltransferase activity. Predicted to be involved in rRNA 2'-O-methylation. Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024864.5. 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
	MRM1	NM_024864.5	MANE Select	c.514G>C	p.Asp172His	missense	Exon 1 of 5	NP_079140.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRM1	ENST00000614766.5	TSL:1 MANE Select	c.514G>C	p.Asp172His	missense	Exon 1 of 5	ENSP00000481559.1	Q6IN84-1
	MRM1	ENST00000612760.1	TSL:1	c.-44+148G>C		intron	N/A	ENSP00000482526.1	A0A087WZC1
	MRM1	ENST00000858970.1		c.514G>C	p.Asp172His	missense	Exon 1 of 5	ENSP00000529029.1

Frequencies

GnomAD3 genomes AF: 0.0000526 AC: 8 AN: 152198 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.0000179 AC: 4 AN: 223514 AF XY: 0.00000819

Gnomad AFR exome AF: 0.000203

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000100

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000421 AC: 6 AN: 1423748 Hom.: 0 Cov.: 32 AF XY: 0.00000427 AC XY: 3 AN XY: 703082

African (AFR) AF: 0.000124 AC: 4 AN: 32388

American (AMR) AF: 0.00 AC: 0 AN: 40886

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23944

East Asian (EAS) AF: 0.00 AC: 0 AN: 39066

South Asian (SAS) AF: 0.00 AC: 0 AN: 82888

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51300

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5600

European-Non Finnish (NFE) AF: 9.18e-7 AC: 1 AN: 1089166

Other (OTH) AF: 0.0000171 AC: 1 AN: 58510

GnomAD4 genome AF: 0.0000525 AC: 8 AN: 152316 Hom.: 0 Cov.: 32 AF XY: 0.0000940 AC XY: 7 AN XY: 74500

African (AFR) AF: 0.000144 AC: 6 AN: 41568

American (AMR) AF: 0.0000654 AC: 1 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

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: 0.00 AC: 0 AN: 68034

Other (OTH) AF: 0.000474 AC: 1 AN: 2110

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000117

ExAC AF: 0.0000167 AC: 2

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Pathogenic	0.34
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.075	T
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Pathogenic	0.98	D
M_CAP	Benign	0.0039	T
MetaRNN	Uncertain	0.72	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
PhyloP100		8.8
PrimateAI	Uncertain	0.64	T
Sift4G	Benign	0.12	T
Polyphen		0.86	P
Vest4		0.81
MVP		0.57
ClinPred		0.97	D
GERP RS		4.9
PromoterAI		-0.068	Neutral
Varity_R		0.72
gMVP		0.84
Mutation Taster		=7/93	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs545927735; hg19: chr17-34958753;