rs6117011

chr20-5942184-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015939.5(TRMT6):c.1027-148G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0483 in 772,334 control chromosomes in the GnomAD database, including 2,292 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.067 (657 hom., cov: 32)
  • Exomes 𝑓: 0.044 (1635 hom.)
• Consequence: TRMT6 NM_015939.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.42

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.224 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRMT6	NM_015939.5	c.1027-148G>A		intron_variant		ENST00000203001.7
TRMT6	NM_001281467.2	c.517-148G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRMT6	ENST00000203001.7	c.1027-148G>A		intron_variant		1	NM_015939.5	P1
TRMT6	ENST00000453074.6	c.517-148G>A		intron_variant		2
TRMT6	ENST00000466974.5	n.1099-148G>A		intron_variant, non_coding_transcript_variant		2
TRMT6	ENST00000473131.5	n.1258-148G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0675 AC: 10264 AN: 152108 Hom.: 656 Cov.: 32

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0749

Gnomad ASJ AF: 0.0372

Gnomad EAS AF: 0.235

Gnomad SAS AF: 0.0843

Gnomad FIN AF: 0.00783

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0194

Gnomad OTH AF: 0.0598

GnomAD4 exome AF: 0.0437 AC: 27068 AN: 620108 Hom.: 1635 AF XY: 0.0443 AC XY: 14555 AN XY: 328308

Gnomad4 AFR exome AF: 0.145

Gnomad4 AMR exome AF: 0.0977

Gnomad4 ASJ exome AF: 0.0293

Gnomad4 EAS exome AF: 0.236

Gnomad4 SAS exome AF: 0.0779

Gnomad4 FIN exome AF: 0.0101

Gnomad4 NFE exome AF: 0.0192

Gnomad4 OTH exome AF: 0.0452

GnomAD4 genome AF: 0.0675 AC: 10272 AN: 152226 Hom.: 657 Cov.: 32 AF XY: 0.0669 AC XY: 4977 AN XY: 74426

Gnomad4 AFR AF: 0.141

Gnomad4 AMR AF: 0.0748

Gnomad4 ASJ AF: 0.0372

Gnomad4 EAS AF: 0.235

Gnomad4 SAS AF: 0.0846

Gnomad4 FIN AF: 0.00783

Gnomad4 NFE AF: 0.0194

Gnomad4 OTH AF: 0.0605

Alfa AF: 0.0439 Hom.: 46

Bravo AF: 0.0781

Asia WGS AF: 0.131 AC: 453 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.33
Dann	Benign	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: rs6117011; hg19: chr20-5922830;