rs369746383

Variant names:

• chr8-13006261-C-A
• rs369746383
• NM_020844.3:c.59C>A

Your query was ambiguous. Multiple possible variants found:

• chr8-13006261-C-A
• chr8-13006261-C-G
• chr8-13006261-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_020844.3(TRMT9B):​c.59C>A​(p.Thr20Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,632 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T20I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TRMT9B NM_020844.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.95

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRMT9B	NM_020844.3	c.59C>A	p.Thr20Lys	missense_variant	Exon 3 of 5	ENST00000524591.7	NP_065895.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRMT9B	ENST00000524591.7	c.59C>A	p.Thr20Lys	missense_variant	Exon 3 of 5	5	NM_020844.3	ENSP00000432695.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000402 AC: 1 AN: 248790 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 134988

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461632 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727094

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

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: 0.00

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
AlphaMissense	Pathogenic	0.83
BayesDel_addAF	Benign	-0.021	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.096	.;T;.;.;.
Eigen	Uncertain	0.65
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.93	D;D;.;D;D
M_CAP	Benign	0.023	T
MetaRNN	Uncertain	0.60	D;D;D;D;D
MetaSVM	Benign	-0.64	T
PrimateAI	Uncertain	0.59	T
PROVEAN	Uncertain	-3.3	D;D;.;.;D
REVEL	Benign	0.26
Sift	Uncertain	0.011	D;D;.;.;D
Sift4G	Uncertain	0.033	D;D;D;D;D
Polyphen		1.0, 1.0	.;D;.;.;D
Vest4		0.64
MutPred		0.63		Gain of ubiquitination at T20 (P = 0.0219);Gain of ubiquitination at T20 (P = 0.0219);Gain of ubiquitination at T20 (P = 0.0219);Gain of ubiquitination at T20 (P = 0.0219);Gain of ubiquitination at T20 (P = 0.0219);
MVP		0.12
ClinPred		0.93	D
GERP RS		5.7
Varity_R		0.30
gMVP		0.67

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: rs369746383; hg19: chr8-12863770;