20-5944573-C-G

Variant names:

• chr20-5944573-C-G
• rs1005517
• NM_015939.5:c.366+232G>C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.111 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRMT6	NM_015939.5	c.366+232G>C		intron_variant	Intron 3 of 10	ENST00000203001.7	NP_057023.2
TRMT6	NM_001281467.2	c.-144-320G>C		intron_variant	Intron 2 of 9		NP_001268396.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRMT6	ENST00000203001.7	c.366+232G>C		intron_variant	Intron 3 of 10	1	NM_015939.5	ENSP00000203001.2

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

Gnomad4 AFR AF: 0.0709

Gnomad4 AMR AF: 0.108

Gnomad4 ASJ AF: 0.0456

Gnomad4 EAS AF: 0.112

Gnomad4 SAS AF: 0.119

Gnomad4 FIN AF: 0.00405

Gnomad4 NFE AF: 0.0149

Gnomad4 OTH AF: 0.0413

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.19
DANN	Benign	0.57

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: rs1005517; hg19: chr20-5925219;