9-97904649-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016481.5(TRMO):c.*84G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.434 in 1,555,454 control chromosomes in the GnomAD database, including 155,757 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.51 (21156 hom., cov: 32)
  • Exomes 𝑓: 0.43 (134601 hom.)
• Consequence: TRMO NM_016481.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.81 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRMO	NM_016481.5	c.*84G>A		3_prime_UTR_variant	5/5	ENST00000375119.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRMO	ENST00000375119.8	c.*84G>A		3_prime_UTR_variant	5/5	1	NM_016481.5	P1
TRMO	ENST00000375118.1	c.*84G>A		3_prime_UTR_variant	2/2	1

Frequencies

GnomAD3 genomes AF: 0.507 AC: 76939 AN: 151900 Hom.: 21114 Cov.: 32

Gnomad AFR AF: 0.689

Gnomad AMI AF: 0.346

Gnomad AMR AF: 0.492

Gnomad ASJ AF: 0.374

Gnomad EAS AF: 0.830

Gnomad SAS AF: 0.574

Gnomad FIN AF: 0.457

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.387

Gnomad OTH AF: 0.465

GnomAD4 exome AF: 0.426 AC: 598309 AN: 1403436 Hom.: 134601 Cov.: 36 AF XY: 0.429 AC XY: 296830 AN XY: 692466

Gnomad4 AFR exome AF: 0.698

Gnomad4 AMR exome AF: 0.548

Gnomad4 ASJ exome AF: 0.378

Gnomad4 EAS exome AF: 0.821

Gnomad4 SAS exome AF: 0.560

Gnomad4 FIN exome AF: 0.443

Gnomad4 NFE exome AF: 0.390

Gnomad4 OTH exome AF: 0.446

GnomAD4 genome AF: 0.507 AC: 77025 AN: 152018 Hom.: 21156 Cov.: 32 AF XY: 0.513 AC XY: 38136 AN XY: 74278

Gnomad4 AFR AF: 0.689

Gnomad4 AMR AF: 0.493

Gnomad4 ASJ AF: 0.374

Gnomad4 EAS AF: 0.831

Gnomad4 SAS AF: 0.573

Gnomad4 FIN AF: 0.457

Gnomad4 NFE AF: 0.387

Gnomad4 OTH AF: 0.466

Alfa AF: 0.412 Hom.: 27531

Bravo AF: 0.517

Asia WGS AF: 0.657 AC: 2287 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	5.2
Dann	Benign	0.78

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: rs6586; hg19: chr9-100666931;