rs2460905

Positions:

• chr8-12977091-G-A

Variant summary

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

The NM_020844.3(TRMT9B):​c.-199-13743G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0828 in 152,224 control chromosomes in the GnomAD database, including 624 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 0.083 (624 hom., cov: 33)
• Consequence: TRMT9B NM_020844.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.490

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 (AFR) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRMT9B	NM_020844.3	c.-199-13743G>A		intron_variant		ENST00000524591.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRMT9B	ENST00000524591.7	c.-199-13743G>A		intron_variant		5	NM_020844.3	P1

Frequencies

GnomAD3 genomes AF: 0.0828 AC: 12594 AN: 152106 Hom.: 622 Cov.: 33

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.0296

Gnomad AMR AF: 0.0454

Gnomad ASJ AF: 0.0646

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.0339

Gnomad FIN AF: 0.0931

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0837

Gnomad OTH AF: 0.0721

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0828 AC: 12606 AN: 152224 Hom.: 624 Cov.: 33 AF XY: 0.0803 AC XY: 5977 AN XY: 74428

Gnomad4 AFR AF: 0.112

Gnomad4 AMR AF: 0.0453

Gnomad4 ASJ AF: 0.0646

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0342

Gnomad4 FIN AF: 0.0931

Gnomad4 NFE AF: 0.0836

Gnomad4 OTH AF: 0.0709

Alfa AF: 0.0880 Hom.: 136

Bravo AF: 0.0805

Asia WGS AF: 0.0240 AC: 85 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	4.8
DANN	Benign	0.51

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: rs2460905; hg19: chr8-12834600;