NM_020844.3:c.116T>G

Variant names:

• chr8-13006318-T-G
• NM_020844.3:c.116T>G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_020844.3(TRMT9B):​c.116T>G​(p.Leu39Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L39V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TRMT9B NM_020844.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.95
• Publications: 0 publications found

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]

LOC124901889 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.862

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020844.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRMT9B	NM_020844.3	MANE Select	c.116T>G	p.Leu39Arg	missense	Exon 3 of 5	NP_065895.2	Q9P272-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRMT9B	ENST00000524591.7	TSL:5 MANE Select	c.116T>G	p.Leu39Arg	missense	Exon 3 of 5	ENSP00000432695.1	Q9P272-1
	TRMT9B	ENST00000855797.1		c.116T>G	p.Leu39Arg	missense	Exon 3 of 5	ENSP00000525856.1
	TRMT9B	ENST00000966194.1		c.116T>G	p.Leu39Arg	missense	Exon 4 of 6	ENSP00000636253.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.32	D
BayesDel_noAF	Pathogenic	0.23
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	T
Eigen	Pathogenic	0.92
Eigen_PC	Pathogenic	0.83
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.87	D
M_CAP	Uncertain	0.24	D
MetaRNN	Pathogenic	0.86	D
MetaSVM	Uncertain	0.26	D
PhyloP100		8.0
PrimateAI	Uncertain	0.74	T
PROVEAN	Pathogenic	-6.0	D
REVEL	Pathogenic	0.69
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.84
MutPred		0.62		Gain of MoRF binding (P = 0.0165)
MVP		0.60
ClinPred		1.0	D
GERP RS		5.7
Varity_R		0.89
gMVP		0.84
Mutation Taster		=36/64	disease causing

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

Other links and lift over

hg19: chr8-12863827;