9-97910061-C-G

Variant names:

• chr9-97910061-C-G
• rs191772878
• NM_016481.5:c.965G>C

Variant summary

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

The NM_016481.5(TRMO):​c.965G>C​(p.Arg322Pro) 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. 14/20 in silico tools predict a benign 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. R322H) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TRMO NM_016481.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.01
• Publications: 0 publications found

Genes affected

TRMO (HGNC:30967): (tRNA methyltransferase O) Enables tRNA (adenine-N6-)-methyltransferase activity. Involved in tRNA methylation. [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=0.08077443).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016481.5. 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
	TRMO	NM_016481.5	MANE Select	c.965G>C	p.Arg322Pro	missense	Exon 4 of 5	NP_057565.3
	TRMO	NM_001371657.1		c.965G>C	p.Arg322Pro	missense	Exon 4 of 6	NP_001358586.1	Q9BU70
	TRMO	NM_001371658.1		c.965G>C	p.Arg322Pro	missense	Exon 4 of 5	NP_001358587.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRMO	ENST00000375119.8	TSL:1 MANE Select	c.965G>C	p.Arg322Pro	missense	Exon 4 of 5	ENSP00000364260.3	Q9BU70
	TRMO	ENST00000375118.1	TSL:1	c.527G>C	p.Arg176Pro	missense	Exon 1 of 2	ENSP00000364259.1	Q5T114
	TRMO	ENST00000864009.1		c.965G>C	p.Arg322Pro	missense	Exon 4 of 6	ENSP00000534068.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	0.022
DANN	Benign	0.73
DEOGEN2	Benign	0.0049	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.033	N
LIST_S2	Benign	0.32	T
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.081	T
MetaSVM	Benign	-1.0	T
PhyloP100		-3.0
PROVEAN	Benign	0.070	N
REVEL	Benign	0.016
Sift	Benign	0.34	T
Sift4G	Benign	0.26	T
Polyphen		0.054	B
Vest4		0.15
MutPred		0.29		Gain of catalytic residue at P321 (P = 0.0164)
MVP		0.061
MPC		0.20
ClinPred		0.13	T
GERP RS		-6.4
Varity_R		0.063
gMVP		0.30
Mutation Taster		=93/7	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: rs191772878; hg19: chr9-100672343;