20-5941981-G-A

Position:

• chr20-5941981-G-A

Variant summary

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

The NM_015939.5(TRMT6):​c.1082C>T​(p.Ala361Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TRMT6 NM_015939.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.79

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.1082C>T	p.Ala361Val	missense_variant	8/11	ENST00000203001.7	NP_057023.2
TRMT6	NM_001281467.2	c.572C>T	p.Ala191Val	missense_variant	7/10		NP_001268396.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRMT6	ENST00000203001.7	c.1082C>T	p.Ala361Val	missense_variant	8/11	1	NM_015939.5	ENSP00000203001.2
TRMT6	ENST00000453074.6	c.572C>T	p.Ala191Val	missense_variant	7/10	2		ENSP00000392070.2
TRMT6	ENST00000466974.5	n.1154C>T		non_coding_transcript_exon_variant	8/9	2
TRMT6	ENST00000473131.5	n.1313C>T		non_coding_transcript_exon_variant	8/11	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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

Jul 10, 2024

The c.1082C>T (p.A361V) alteration is located in exon 8 (coding exon 8) of the TRMT6 gene. This alteration results from a C to T substitution at nucleotide position 1082, causing the alanine (A) at amino acid position 361 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	Benign	0.17
BayesDel_addAF	Uncertain	0.061	T
BayesDel_noAF	Benign	-0.15
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.016	T;.
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.85	T;T
M_CAP	Benign	0.030	D
MetaRNN	Uncertain	0.56	D;D
MetaSVM	Benign	-1.2	T
MutationAssessor	Benign	1.5	L;.
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-1.2	N;N
REVEL	Benign	0.25
Sift	Benign	0.041	D;D
Sift4G	Uncertain	0.045	D;T
Polyphen		0.90	P;.
Vest4		0.61
MutPred		0.56		Loss of disorder (P = 0.0682);.;
MVP		0.41
MPC		0.37
ClinPred		0.96	D
GERP RS		6.2
Varity_R		0.44
gMVP		0.40

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: chr20-5922627;