20-5944573-C-G

Variant names:

• chr20-5944573-C-G
• rs1005517
• NM_015939.5:c.366+232G>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.366+232G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0464 in 152,266 control chromosomes in the GnomAD database, including 304 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 0.046 (304 hom., cov: 33)
• Consequence: TRMT6 NM_015939.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.483
• Publications: 0 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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.111 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRMT6	NM_015939.5	MANE Select	c.366+232G>C		intron	N/A	NP_057023.2
	TRMT6	NM_001281467.2		c.-144-320G>C		intron	N/A	NP_001268396.1	Q9UJA5-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRMT6	ENST00000203001.7	TSL:1 MANE Select	c.366+232G>C		intron	N/A	ENSP00000203001.2	Q9UJA5-1
	TRMT6	ENST00000931286.1		c.366+232G>C		intron	N/A	ENSP00000601345.1
	TRMT6	ENST00000931288.1		c.366+232G>C		intron	N/A	ENSP00000601347.1

Frequencies

GnomAD3 genomes AF: 0.0464 AC: 7061 AN: 152148 Hom.: 305 Cov.: 33

Gnomad AFR AF: 0.0710

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.0456

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.00405

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0149

Gnomad OTH AF: 0.0417

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0464 AC: 7065 AN: 152266 Hom.: 304 Cov.: 33 AF XY: 0.0493 AC XY: 3670 AN XY: 74450

African (AFR) AF: 0.0709 AC: 2947 AN: 41562

American (AMR) AF: 0.108 AC: 1646 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0456 AC: 158 AN: 3468

East Asian (EAS) AF: 0.112 AC: 580 AN: 5180

South Asian (SAS) AF: 0.119 AC: 571 AN: 4816

European-Finnish (FIN) AF: 0.00405 AC: 43 AN: 10610

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0149 AC: 1016 AN: 68026

Other (OTH) AF: 0.0413 AC: 87 AN: 2108

Alfa AF: 0.00544 Hom.: 1

Bravo AF: 0.0532

Asia WGS AF: 0.123 AC: 426 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.19
DANN	Benign	0.57
PhyloP100		-0.48
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1005517; hg19: chr20-5925219;