chr9-97910149-C-T

Variant names:

• chr9-97910149-C-T
• NM_016481.5:c.877G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_016481.5(TRMO):​c.877G>A​(p.Glu293Lys) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TRMO NM_016481.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.107
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06118563).

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.877G>A	p.Glu293Lys	missense	Exon 4 of 5	NP_057565.3
	TRMO	NM_001371657.1		c.877G>A	p.Glu293Lys	missense	Exon 4 of 6	NP_001358586.1	Q9BU70
	TRMO	NM_001371658.1		c.877G>A	p.Glu293Lys	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.877G>A	p.Glu293Lys	missense	Exon 4 of 5	ENSP00000364260.3	Q9BU70
	TRMO	ENST00000375118.1	TSL:1	c.439G>A	p.Glu147Lys	missense	Exon 1 of 2	ENSP00000364259.1	Q5T114
	TRMO	ENST00000864009.1		c.877G>A	p.Glu293Lys	missense	Exon 4 of 6	ENSP00000534068.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

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	0.075
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	6.4
DANN	Benign	0.92
DEOGEN2	Benign	0.012	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.47	T
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.061	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.11
PROVEAN	Benign	-0.98	N
REVEL	Benign	0.0080
Sift	Benign	0.14	T
Sift4G	Benign	0.22	T
Polyphen		0.0	B
Vest4		0.073
MutPred		0.36		Gain of MoRF binding (P = 0.0028)
MVP		0.10
MPC		0.14
ClinPred		0.030	T
GERP RS		-0.013
Varity_R		0.030
gMVP		0.31
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

hg19: chr9-100672431;