9-97910149-C-T

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -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. 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)
• Consequence: TRMO NM_016481.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.107

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

Verdict is Likely_benign. Variant got -2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRMO	NM_016481.5	c.877G>A	p.Glu293Lys	missense_variant	Exon 4 of 5	ENST00000375119.8	NP_057565.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRMO	ENST00000375119.8	c.877G>A	p.Glu293Lys	missense_variant	Exon 4 of 5	1	NM_016481.5	ENSP00000364260.3
TRMO	ENST00000375118.1	c.439G>A	p.Glu147Lys	missense_variant	Exon 1 of 2	1		ENSP00000364259.1
TRMO	ENST00000478126.5	n.681G>A		non_coding_transcript_exon_variant	Exon 3 of 3	2
TRMO	ENST00000375117.8	c.*497G>A		downstream_gene_variant		3		ENSP00000364258.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 10, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.877G>A (p.E293K) alteration is located in exon 4 (coding exon 4) of the TRMO gene. This alteration results from a G to A substitution at nucleotide position 877, causing the glutamic acid (E) at amino acid position 293 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.47	T;T
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.061	T;T
MetaSVM	Benign	-1.0	T
PROVEAN	Benign	-0.98	N;N
REVEL	Benign	0.0080
Sift	Benign	0.14	T;T
Sift4G	Benign	0.22	T;T
Polyphen		0.0	B;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

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-100672431;