chr20-5942556-G-C

Position:

• chr20-5942556-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_015939.5(TRMT6):​c.898C>G​(p.Gln300Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TRMT6 NM_015939.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.03

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 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=0.060573697).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRMT6	NM_015939.5	c.898C>G	p.Gln300Glu	missense_variant	7/11	ENST00000203001.7	NP_057023.2
TRMT6	NM_001281467.2	c.388C>G	p.Gln130Glu	missense_variant	6/10		NP_001268396.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRMT6	ENST00000203001.7	c.898C>G	p.Gln300Glu	missense_variant	7/11	1	NM_015939.5	ENSP00000203001.2
TRMT6	ENST00000453074.6	c.388C>G	p.Gln130Glu	missense_variant	6/10	2		ENSP00000392070.2
TRMT6	ENST00000466974.5	n.970C>G		non_coding_transcript_exon_variant	7/9	2
TRMT6	ENST00000473131.5	n.1129C>G		non_coding_transcript_exon_variant	7/11	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

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

Jun 10, 2024

The c.898C>G (p.Q300E) alteration is located in exon 7 (coding exon 7) of the TRMT6 gene. This alteration results from a C to G substitution at nucleotide position 898, causing the glutamine (Q) at amino acid position 300 to be replaced by a glutamic acid (E). 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	0.059
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	16
DANN	Benign	0.63
DEOGEN2	Benign	0.0045	T;.
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.24
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.68	T;T
M_CAP	Benign	0.0069	T
MetaRNN	Benign	0.061	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N;.
PrimateAI	Benign	0.30	T
PROVEAN	Benign	0.17	N;N
REVEL	Benign	0.067
Sift	Benign	0.87	T;T
Sift4G	Benign	0.96	T;T
Polyphen		0.0020	B;.
Vest4		0.32
MutPred		0.30		Gain of helix (P = 0.0854);.;
MVP		0.30
MPC		0.32
ClinPred		0.16	T
GERP RS		4.0
Varity_R		0.060
gMVP		0.25

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: chr20-5923202;