8-13006317-C-G

Position:

• chr8-13006317-C-G

Variant summary

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

The NM_020844.3(TRMT9B):​c.115C>G​(p.Leu39Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar 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: 4.98

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/exons	MANE	Protein	UniProt
TRMT9B	NM_020844.3	c.115C>G	p.Leu39Val	missense_variant	3/5	ENST00000524591.7	NP_065895.2
LOC124901889	XR_007060825.1	n.491+8023G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRMT9B	ENST00000524591.7	c.115C>G	p.Leu39Val	missense_variant	3/5	5	NM_020844.3	ENSP00000432695	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 15, 2022

The c.115C>G (p.L39V) alteration is located in exon 3 (coding exon 1) of the KIAA1456 gene. This alteration results from a C to G substitution at nucleotide position 115, causing the leucine (L) at amino acid position 39 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.53
BayesDel_addAF	Uncertain	0.026	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	.;T;.;.;.
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.87	D;D;.;D;D
M_CAP	Benign	0.035	D
MetaRNN	Uncertain	0.45	T;T;T;T;T
MetaSVM	Benign	-0.48	T
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.65	T
PROVEAN	Uncertain	-2.9	D;D;.;.;D
REVEL	Benign	0.20
Sift	Benign	0.049	D;D;.;.;D
Sift4G	Uncertain	0.010	D;D;D;D;T
Polyphen		1.0, 0.99	.;D;.;.;D
Vest4		0.60
MutPred		0.48		Gain of methylation at K43 (P = 0.086);Gain of methylation at K43 (P = 0.086);Gain of methylation at K43 (P = 0.086);Gain of methylation at K43 (P = 0.086);Gain of methylation at K43 (P = 0.086);
MVP		0.28
ClinPred		0.97	D
GERP RS		4.8
Varity_R		0.44
gMVP		0.46

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: chr8-12863826;