chr20-5941263-C-G

Position:

• chr20-5941263-C-G

Variant summary

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

The NM_015939.5(TRMT6):​c.1195G>C​(p.Val399Leu) 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: TRMT6 NM_015939.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.85

Genes affected

TRMT6 (HGNC:20900): (tRNA methyltransferase 6 non-catalytic subunit) This gene encodes a member of the tRNA methyltransferase 6 protein family. A similar protein in yeast is part of a two component methyltransferase, which is involved in the posttranslational modification that produces the modified nucleoside 1-methyladenosine in tRNAs. Modified 1-methyladenosine influences initiator methionine stability and may be involved in the replication of human immunodeficiency virus type 1. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

TRMT6 (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
TRMT6	NM_015939.5	c.1195G>C	p.Val399Leu	missense_variant	9/11	ENST00000203001.7	NP_057023.2
TRMT6	NM_001281467.2	c.685G>C	p.Val229Leu	missense_variant	8/10		NP_001268396.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRMT6	ENST00000203001.7	c.1195G>C	p.Val399Leu	missense_variant	9/11	1	NM_015939.5	ENSP00000203001.2
TRMT6	ENST00000453074.6	c.685G>C	p.Val229Leu	missense_variant	8/10	2		ENSP00000392070.2
TRMT6	ENST00000466974.5	n.1872G>C		non_coding_transcript_exon_variant	8/9	2
TRMT6	ENST00000473131.5	n.1426G>C		non_coding_transcript_exon_variant	9/11	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

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

May 20, 2024

The c.1195G>C (p.V399L) alteration is located in exon 9 (coding exon 9) of the TRMT6 gene. This alteration results from a G to C substitution at nucleotide position 1195, causing the valine (V) at amino acid position 399 to be replaced by a leucine (L). 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	0.56
BayesDel_addAF	Benign	-0.021	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.066	T;.
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.91	D;D
M_CAP	Benign	0.050	D
MetaRNN	Uncertain	0.65	D;D
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.6	M;.
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-1.8	N;N
REVEL	Benign	0.10
Sift	Uncertain	0.011	D;D
Sift4G	Uncertain	0.024	D;D
Polyphen		0.65	P;.
Vest4		0.68
MutPred		0.57		Loss of methylation at K404 (P = 0.0802);.;
MVP		0.47
MPC		0.59
ClinPred		0.89	D
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.55
gMVP		0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr20-5921909;