chr8-13006209-C-G

Variant names:

• chr8-13006209-C-G
• NM_020844.3:c.7C>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.7C>G​(p.His3Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,512 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. 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. H3Y) 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: 0.351

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.034846067).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRMT9B	NM_020844.3	c.7C>G	p.His3Asp	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.7C>G	p.His3Asp	missense_variant	Exon 3 of 5	5	NM_020844.3	ENSP00000432695.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461512 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727030

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	6.7
DANN	Uncertain	0.98
DEOGEN2	Benign	0.022	.;T;.;.;.
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.56
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.50	T;T;.;T;T
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.035	T;T;T;T;T
MetaSVM	Benign	-0.98	T
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.3	N;N;.;.;N
REVEL	Benign	0.021
Sift	Uncertain	0.023	D;T;.;.;D
Sift4G	Benign	0.080	T;T;T;T;T
Polyphen		0.0020, 0.026	.;B;.;.;B
Vest4		0.38
MutPred		0.26		Loss of disorder (P = 0.3336);Loss of disorder (P = 0.3336);Loss of disorder (P = 0.3336);Loss of disorder (P = 0.3336);Loss of disorder (P = 0.3336);
MVP		0.030
ClinPred		0.047	T
GERP RS		2.6
Varity_R		0.085
gMVP		0.49

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-12863718;