17-36602324-G-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_024864.5(MRM1):​c.514G>T​(p.Asp172Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000702 in 1,423,748 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D172H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: MRM1 NM_024864.5 missense
• Clinical Significance: Not reported in ClinVar
• 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.869

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>T	p.Asp172Tyr	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>T	p.Asp172Tyr	missense	Exon 1 of 5	ENSP00000481559.1	Q6IN84-1
	MRM1	ENST00000612760.1	TSL:1	c.-44+148G>T		intron	N/A	ENSP00000482526.1	A0A087WZC1
	MRM1	ENST00000858970.1		c.514G>T	p.Asp172Tyr	missense	Exon 1 of 5	ENSP00000529029.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.02e-7 AC: 1 AN: 1423748 Hom.: 0 Cov.: 32 AF XY: 0.00000142 AC XY: 1 AN XY: 703082

African (AFR) AF: 0.00 AC: 0 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: 0.0000256 AC: 1 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: 0.00 AC: 0 AN: 1089166

Other (OTH) AF: 0.00 AC: 0 AN: 58510

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Pathogenic	0.51	D
BayesDel_noAF	Pathogenic	0.49
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	T
Eigen	Pathogenic	0.99
Eigen_PC	Pathogenic	0.89
FATHMM_MKL	Pathogenic	0.97	D
M_CAP	Benign	0.010	T
MetaRNN	Pathogenic	0.87	D
MetaSVM	Uncertain	-0.054	T
MutationAssessor	Pathogenic	3.8	H
PhyloP100		8.8
PrimateAI	Uncertain	0.63	T
Sift4G	Uncertain	0.012	D
Polyphen		1.0	D
Vest4		0.89
MutPred		0.61		Gain of phosphorylation at D172 (P = 0.0339)
MVP		0.76
ClinPred		0.99	D
GERP RS		4.9
PromoterAI		-0.0071	Neutral
Varity_R		0.72
gMVP		0.86

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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;