8-12962330-T-C

Position:

• chr8-12962330-T-C

Variant summary

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

The NM_020844.3(TRMT9B):​c.-200+16364T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.413 in 152,102 control chromosomes in the GnomAD database, including 13,829 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 0.41 (13829 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TRMT9B NM_020844.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0690

Genes affected

TRMT9B (HGNC:26725): (tRNA methyltransferase 9B (putative)) Enables tRNA methyltransferase activity. Predicted to be involved in tRNA wobble uridine modification. Predicted to be active in cytoplasm and nucleus. [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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.499 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRMT9B	NM_020844.3	c.-200+16364T>C		intron_variant		ENST00000524591.7	NP_065895.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRMT9B	ENST00000524591.7	c.-200+16364T>C		intron_variant		5	NM_020844.3	ENSP00000432695	P1

Frequencies

GnomAD3 genomes AF: 0.413 AC: 62827 AN: 151984 Hom.: 13814 Cov.: 33

Gnomad AFR AF: 0.308

Gnomad AMI AF: 0.644

Gnomad AMR AF: 0.328

Gnomad ASJ AF: 0.547

Gnomad EAS AF: 0.0931

Gnomad SAS AF: 0.481

Gnomad FIN AF: 0.425

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.503

Gnomad OTH AF: 0.443

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.413 AC: 62865 AN: 152102 Hom.: 13829 Cov.: 33 AF XY: 0.410 AC XY: 30454 AN XY: 74356

Gnomad4 AFR AF: 0.308

Gnomad4 AMR AF: 0.328

Gnomad4 ASJ AF: 0.547

Gnomad4 EAS AF: 0.0925

Gnomad4 SAS AF: 0.481

Gnomad4 FIN AF: 0.425

Gnomad4 NFE AF: 0.503

Gnomad4 OTH AF: 0.440

Alfa AF: 0.426 Hom.: 2746

Bravo AF: 0.397

Asia WGS AF: 0.300 AC: 1049 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.8
DANN	Benign	0.41

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: rs2203837; hg19: chr8-12819839;