9-97910230-C-T

Variant names:

• chr9-97910230-C-T
• rs150271508
• NM_016481.5:c.796G>A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_016481.5(TRMO):​c.796G>A​(p.Val266Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000465 in 1,614,198 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 Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00028 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00048 (0 hom.)
• Consequence: TRMO NM_016481.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0980

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 -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.020136118).
• BP6: Variant 9-97910230-C-T is Benign according to our data. Variant chr9-97910230-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3182970.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRMO	NM_016481.5	c.796G>A	p.Val266Met	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.796G>A	p.Val266Met	missense_variant	Exon 4 of 5	1	NM_016481.5	ENSP00000364260.3
TRMO	ENST00000375118.1	c.358G>A	p.Val120Met	missense_variant	Exon 1 of 2	1		ENSP00000364259.1
TRMO	ENST00000478126.5	n.600G>A		non_coding_transcript_exon_variant	Exon 3 of 3	2
TRMO	ENST00000375117.8	c.*416G>A		downstream_gene_variant		3		ENSP00000364258.4

Frequencies

GnomAD3 genomes AF: 0.000283 AC: 43 AN: 152190 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000515

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000179 AC: 45 AN: 251486 Hom.: 0 AF XY: 0.000199 AC XY: 27 AN XY: 135914

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000578

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000653

Gnomad FIN exome AF: 0.0000924

Gnomad NFE exome AF: 0.000343

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000484 AC: 707 AN: 1461890 Hom.: 0 Cov.: 33 AF XY: 0.000458 AC XY: 333 AN XY: 727246

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.0000894

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.0000562

Gnomad4 NFE exome AF: 0.000599

Gnomad4 OTH exome AF: 0.000331

GnomAD4 genome AF: 0.000282 AC: 43 AN: 152308 Hom.: 0 Cov.: 32 AF XY: 0.000242 AC XY: 18 AN XY: 74480

Gnomad4 AFR AF: 0.0000962

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000515

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000465 Hom.: 0

Bravo AF: 0.000310

TwinsUK AF: 0.00135 AC: 5

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.000157 AC: 19

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.000709

EpiControl AF: 0.000711

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Aug 13, 2021

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	6.5
DANN	Benign	0.68
DEOGEN2	Benign	0.013	T;T;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.039	N
LIST_S2	Benign	0.63	T;T;T
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.020	T;T;T
MetaSVM	Benign	-0.97	T
PROVEAN	Benign	-0.53	N;N;.
REVEL	Benign	0.054
Sift	Benign	0.31	T;T;.
Sift4G	Benign	0.13	T;T;T
Polyphen		0.49	P;P;B
Vest4		0.076
MVP		0.067
MPC		0.15
ClinPred		0.017	T
GERP RS		-0.29
Varity_R		0.015
gMVP		0.13

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

Publications

LitVar

Other links and lift over

dbSNP: rs150271508; hg19: chr9-100672512; COSMIC: COSV64292104; COSMIC: COSV64292104;