chr17-36601821-T-C

Variant names:

• chr17-36601821-T-C
• rs779554507
• NM_024864.5:c.11T>C

Variant summary

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

The NM_024864.5(MRM1):​c.11T>C​(p.Leu4Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000777 in 1,415,148 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000078 (0 hom.)
• Consequence: MRM1 NM_024864.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.630
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.078005284).

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.11T>C	p.Leu4Pro	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.11T>C	p.Leu4Pro	missense	Exon 1 of 5	ENSP00000481559.1	Q6IN84-1
	MRM1	ENST00000858970.1		c.11T>C	p.Leu4Pro	missense	Exon 1 of 5	ENSP00000529029.1
	MRM1	ENST00000940336.1		c.11T>C	p.Leu4Pro	missense	Exon 1 of 4	ENSP00000610395.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000777 AC: 11 AN: 1415148 Hom.: 0 Cov.: 31 AF XY: 0.00000858 AC XY: 6 AN XY: 699052

African (AFR) AF: 0.00 AC: 0 AN: 32792

American (AMR) AF: 0.00 AC: 0 AN: 41886

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23394

East Asian (EAS) AF: 0.00 AC: 0 AN: 39228

South Asian (SAS) AF: 0.00 AC: 0 AN: 80088

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42794

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5448

European-Non Finnish (NFE) AF: 0.0000101 AC: 11 AN: 1090974

Other (OTH) AF: 0.00 AC: 0 AN: 58544

GnomAD4 genome Cov.: 32

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	0.070
BayesDel_addAF	Benign	-0.053	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	13
DANN	Benign	0.70
DEOGEN2	Benign	0.011	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.12	N
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.078	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L
PhyloP100		0.63
PrimateAI	Uncertain	0.61	T
Sift4G	Benign	0.095	T
Polyphen		0.0050	B
Vest4		0.36
MutPred		0.48		Loss of stability (P = 0.0051)
MVP		0.27
ClinPred		0.079	T
GERP RS		0.68
PromoterAI		-0.043	Neutral
Varity_R		0.19
gMVP		0.65
Mutation Taster		=100/0	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: rs779554507; hg19: chr17-34958250;