9-97913495-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BA1

The NM_016481.5(TRMO):c.315G>A(p.Arg105=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00264 in 1,614,036 control chromosomes in the GnomAD database, including 98 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0025 (7 hom., cov: 31)
  • Exomes 𝑓: 0.0027 (91 hom.)
• Consequence: TRMO NM_016481.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.251

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).
• BP6: Variant 9-97913495-C-T is Benign according to our data. Variant chr9-97913495-C-T is described in ClinVar as [Benign]. Clinvar id is 773782.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.251 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0514 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRMO	NM_016481.5	c.315G>A	p.Arg105=	synonymous_variant	3/5	ENST00000375119.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRMO	ENST00000375119.8	c.315G>A	p.Arg105=	synonymous_variant	3/5	1	NM_016481.5	P1

Frequencies

GnomAD3 genomes AF: 0.00249 AC: 379 AN: 152088 Hom.: 7 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00131

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.0575

Gnomad SAS AF: 0.0112

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.00598 AC: 1503 AN: 251414 Hom.: 26 AF XY: 0.00595 AC XY: 808 AN XY: 135882

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.00390

Gnomad ASJ exome AF: 0.000595

Gnomad EAS exome AF: 0.0544

Gnomad SAS exome AF: 0.0109

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000616

Gnomad OTH exome AF: 0.00326

GnomAD4 exome AF: 0.00266 AC: 3895 AN: 1461828 Hom.: 91 Cov.: 31 AF XY: 0.00290 AC XY: 2107 AN XY: 727206

Gnomad4 AFR exome AF: 0.0000597

Gnomad4 AMR exome AF: 0.00369

Gnomad4 ASJ exome AF: 0.000689

Gnomad4 EAS exome AF: 0.0639

Gnomad4 SAS exome AF: 0.0109

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000414

Gnomad4 OTH exome AF: 0.00298

GnomAD4 genome AF: 0.00245 AC: 373 AN: 152208 Hom.: 7 Cov.: 31 AF XY: 0.00308 AC XY: 229 AN XY: 74398

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00131

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.0567

Gnomad4 SAS AF: 0.0110

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000588

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000309 Hom.: 1

Bravo AF: 0.00287

Asia WGS AF: 0.0210 AC: 74 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Mar 30, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
Cadd	Benign	9.8
Dann	Benign	0.73

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: rs77668890; hg19: chr9-100675777; COSMIC: COSV63336959; COSMIC: COSV63336959;