rs10485494

Positions:

• chr20-5938732-C-G

Variant summary

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

The NM_015939.5(TRMT6):​c.1303-6G>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0452 in 1,612,808 control chromosomes in the GnomAD database, including 1,783 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.050 (206 hom., cov: 32)
  • Exomes 𝑓: 0.045 (1577 hom.)
• Consequence: TRMT6 NM_015939.5 splice_region, intron
• Scores: Splicing: ADA: 0.0001885
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.519

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0636 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRMT6	NM_015939.5	c.1303-6G>C		splice_region_variant, intron_variant		ENST00000203001.7	NP_057023.2
TRMT6	NM_001281467.2	c.793-6G>C		splice_region_variant, intron_variant			NP_001268396.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRMT6	ENST00000203001.7	c.1303-6G>C		splice_region_variant, intron_variant		1	NM_015939.5	ENSP00000203001.2
TRMT6	ENST00000453074.6	c.793-6G>C		splice_region_variant, intron_variant		2		ENSP00000392070.2
TRMT6	ENST00000466974.5	n.2083-6G>C		splice_region_variant, intron_variant		2
TRMT6	ENST00000473131.5	n.1534-6G>C		splice_region_variant, intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0499 AC: 7587 AN: 152168 Hom.: 206 Cov.: 32

Gnomad AFR AF: 0.0655

Gnomad AMI AF: 0.0658

Gnomad AMR AF: 0.0464

Gnomad ASJ AF: 0.0726

Gnomad EAS AF: 0.00712

Gnomad SAS AF: 0.0228

Gnomad FIN AF: 0.0314

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0471

Gnomad OTH AF: 0.0664

GnomAD3 exomes AF: 0.0415 AC: 10391 AN: 250268 Hom.: 292 AF XY: 0.0420 AC XY: 5676 AN XY: 135256

Gnomad AFR exome AF: 0.0685

Gnomad AMR exome AF: 0.0323

Gnomad ASJ exome AF: 0.0644

Gnomad EAS exome AF: 0.00675

Gnomad SAS exome AF: 0.0208

Gnomad FIN exome AF: 0.0252

Gnomad NFE exome AF: 0.0522

Gnomad OTH exome AF: 0.0519

GnomAD4 exome AF: 0.0448 AC: 65367 AN: 1460522 Hom.: 1577 Cov.: 30 AF XY: 0.0444 AC XY: 32262 AN XY: 726562

Gnomad4 AFR exome AF: 0.0677

Gnomad4 AMR exome AF: 0.0350

Gnomad4 ASJ exome AF: 0.0649

Gnomad4 EAS exome AF: 0.00691

Gnomad4 SAS exome AF: 0.0221

Gnomad4 FIN exome AF: 0.0271

Gnomad4 NFE exome AF: 0.0477

Gnomad4 OTH exome AF: 0.0470

GnomAD4 genome AF: 0.0499 AC: 7600 AN: 152286 Hom.: 206 Cov.: 32 AF XY: 0.0492 AC XY: 3661 AN XY: 74464

Gnomad4 AFR AF: 0.0656

Gnomad4 AMR AF: 0.0462

Gnomad4 ASJ AF: 0.0726

Gnomad4 EAS AF: 0.00732

Gnomad4 SAS AF: 0.0228

Gnomad4 FIN AF: 0.0314

Gnomad4 NFE AF: 0.0471

Gnomad4 OTH AF: 0.0657

Alfa AF: 0.0508 Hom.: 85

Bravo AF: 0.0525

Asia WGS AF: 0.0200 AC: 71 AN: 3478

EpiCase AF: 0.0558

EpiControl AF: 0.0592

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	6.5
DANN	Benign	0.72

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00019
dbscSNV1_RF	Benign	0.0060
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: rs10485494; hg19: chr20-5919378;