8-13006313-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_020844.3(TRMT9B):c.111G>C(p.Gln37His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 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: 3.98

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31662402).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRMT9B	NM_020844.3	c.111G>C	p.Gln37His	missense_variant	3/5	ENST00000524591.7
LOC124901889	XR_007060825.1	n.491+8027C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRMT9B	ENST00000524591.7	c.111G>C	p.Gln37His	missense_variant	3/5	5	NM_020844.3	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

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

Oct 06, 2022

The c.111G>C (p.Q37H) alteration is located in exon 3 (coding exon 1) of the KIAA1456 gene. This alteration results from a G to C substitution at nucleotide position 111, causing the glutamine (Q) at amino acid position 37 to be replaced by a histidine (H). 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	Benign	0.32
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
Cadd	Benign	21
Dann	Uncertain	1.0
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.81	T;T;.;T;T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.32	T;T;T;T;T
MetaSVM	Benign	-0.82	T
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.54	T
PROVEAN	Uncertain	-2.6	D;D;.;.;D
REVEL	Benign	0.13
Sift	Uncertain	0.024	D;D;.;.;D
Sift4G	Uncertain	0.0080	D;D;D;D;D
Polyphen		1.0, 1.0	.;D;.;.;D
Vest4		0.36
MutPred		0.33		Loss of MoRF binding (P = 0.1019);Loss of MoRF binding (P = 0.1019);Loss of MoRF binding (P = 0.1019);Loss of MoRF binding (P = 0.1019);Loss of MoRF binding (P = 0.1019);
MVP		0.20
ClinPred		0.96	D
GERP RS		3.6
Varity_R		0.20
gMVP		0.39

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: rs1036248012; hg19: chr8-12863822;