rs10485494

Variant names:

• chr20-5938732-C-G
• rs10485494
• NM_015939.5:c.1303-6G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015939.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRMT6	NM_015939.5	MANE Select	c.1303-6G>C		splice_region intron	N/A	NP_057023.2
	TRMT6	NM_001281467.2		c.793-6G>C		splice_region intron	N/A	NP_001268396.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRMT6	ENST00000203001.7	TSL:1 MANE Select	c.1303-6G>C		splice_region intron	N/A	ENSP00000203001.2
	TRMT6	ENST00000453074.6	TSL:2	c.793-6G>C		splice_region intron	N/A	ENSP00000392070.2
	TRMT6	ENST00000466974.5	TSL:2	n.2083-6G>C		splice_region intron	N/A

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

GnomAD2 exomes AF: 0.0415 AC: 10391 AN: 250268 AF XY: 0.0420

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 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

African (AFR) AF: 0.0677 AC: 2261 AN: 33412

American (AMR) AF: 0.0350 AC: 1556 AN: 44508

Ashkenazi Jewish (ASJ) AF: 0.0649 AC: 1691 AN: 26064

East Asian (EAS) AF: 0.00691 AC: 274 AN: 39674

South Asian (SAS) AF: 0.0221 AC: 1903 AN: 86150

European-Finnish (FIN) AF: 0.0271 AC: 1445 AN: 53396

Middle Eastern (MID) AF: 0.0696 AC: 401 AN: 5760

European-Non Finnish (NFE) AF: 0.0477 AC: 52998 AN: 1111222

Other (OTH) AF: 0.0470 AC: 2838 AN: 60336

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

African (AFR) AF: 0.0656 AC: 2727 AN: 41558

American (AMR) AF: 0.0462 AC: 706 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0726 AC: 252 AN: 3470

East Asian (EAS) AF: 0.00732 AC: 38 AN: 5188

South Asian (SAS) AF: 0.0228 AC: 110 AN: 4828

European-Finnish (FIN) AF: 0.0314 AC: 333 AN: 10614

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.0471 AC: 3206 AN: 68016

Other (OTH) AF: 0.0657 AC: 139 AN: 2116

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	6.5
DANN	Benign	0.72
PhyloP100		-0.52
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10485494; hg19: chr20-5919378;