Variant chr8-13021032-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_020844.3(TRMT9B):c.353A>G(p.Gln118Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000497 in 1,409,536 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000050 ( 0 hom. )

Consequence

TRMT9B
NM_020844.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.92

Variant links:

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]

TRMT9B links:

LOC124901889 (HGNC:):

LOC124901889 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12518713).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRMT9B	NM_020844.3 linkuse as main transcript	c.353A>G	p.Gln118Arg	missense_variant	5/5	ENST00000524591.7	NP_065895.2
LOC124901889	XR_007060825.1 linkuse as main transcript	n.369-6570T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRMT9B	ENST00000524591.7 linkuse as main transcript	c.353A>G	p.Gln118Arg	missense_variant	5/5	5	NM_020844.3	ENSP00000432695	P1	Q9P272-1
TRMT9B	ENST00000529978.1 linkuse as main transcript	n.870A>G		non_coding_transcript_exon_variant	2/2	1
TRMT9B	ENST00000447063.6 linkuse as main transcript	c.264+8239A>G		intron_variant		2		ENSP00000443288
TRMT9B	ENST00000529706.1 linkuse as main transcript	n.2557A>G		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000497

AC:

AN:

1409536

Hom.:

Cov.:

AF XY:

0.00000573

AC XY:

AN XY:

697552

show subpopulations

Gnomad4 AFR exome

AF:

0.000188

Gnomad4 AMR exome

AF:

0.00

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:

0.0000172

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 25, 2023

The c.353A>G (p.Q118R) alteration is located in exon 5 (coding exon 3) of the KIAA1456 gene. This alteration results from a A to G substitution at nucleotide position 353, causing the glutamine (Q) at amino acid position 118 to be replaced by an arginine (R). 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

0.13

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.029

Eigen

Benign

-0.16

Eigen_PC

Benign

-0.029

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.72

M_CAP

Benign

0.019

MetaRNN

Benign

0.13

MetaSVM

Benign

-1.0

MutationTaster

Benign

0.58

D;D

PrimateAI

Benign

0.46

PROVEAN

Benign

-2.3

REVEL

Benign

0.088

Sift

Benign

0.051

Sift4G

Benign

0.11

Polyphen

0.32

Vest4

0.14

MutPred

0.50

Gain of MoRF binding (P = 0.0593);

MVP

0.076

ClinPred

0.92

GERP RS

3.0

Varity_R

0.16

gMVP

0.35

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over