rs13251099

Positions:

• chr8-12952059-A-G

Variant summary

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

The NM_020844.3(TRMT9B):​c.-200+6093A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000603 in 165,900 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000060 (0 hom.)
• Consequence: TRMT9B NM_020844.3 intron
• Scores: Splicing: ADA: 0.0002223
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.137

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRMT9B	NM_020844.3	c.-200+6093A>G		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+6093A>G		intron_variant		5	NM_020844.3	ENSP00000432695.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000603 AC: 1 AN: 165900 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 94838

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000116

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	13
DANN	Benign	0.83

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00022
dbscSNV1_RF	Benign	0.032
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

LitVar

Other links and lift over

dbSNP: rs13251099; hg19: chr8-12809568;