20-5944037-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_015939.5(TRMT6):c.459-6C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00543 in 1,566,742 control chromosomes in the GnomAD database, including 397 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.028 (187 hom., cov: 32)
  • Exomes 𝑓: 0.0031 (210 hom.)
• Consequence: TRMT6 NM_015939.5 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.0001074
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0400

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 20-5944037-G-A is Benign according to our data. Variant chr20-5944037-G-A is described in ClinVar as [Benign]. Clinvar id is 769075.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.093 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRMT6	NM_015939.5	c.459-6C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000203001.7
TRMT6	NM_001281467.2	c.-52-6C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRMT6	ENST00000203001.7	c.459-6C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_015939.5	P1

Frequencies

GnomAD3 genomes AF: 0.0276 AC: 4178 AN: 151210 Hom.: 185 Cov.: 32

Gnomad AFR AF: 0.0956

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0113

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000209

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.000663

Gnomad OTH AF: 0.0192

GnomAD3 exomes AF: 0.00795 AC: 1845 AN: 232094 Hom.: 91 AF XY: 0.00570 AC XY: 718 AN XY: 125992

Gnomad AFR exome AF: 0.101

Gnomad AMR exome AF: 0.00618

Gnomad ASJ exome AF: 0.000110

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000335

Gnomad FIN exome AF: 0.0000469

Gnomad NFE exome AF: 0.000518

Gnomad OTH exome AF: 0.00688

GnomAD4 exome AF: 0.00306 AC: 4329 AN: 1415414 Hom.: 210 Cov.: 30 AF XY: 0.00271 AC XY: 1905 AN XY: 702548

Gnomad4 AFR exome AF: 0.0998

Gnomad4 AMR exome AF: 0.00681

Gnomad4 ASJ exome AF: 0.0000402

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000241

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000301

Gnomad4 OTH exome AF: 0.00806

GnomAD4 genome AF: 0.0277 AC: 4185 AN: 151328 Hom.: 187 Cov.: 32 AF XY: 0.0260 AC XY: 1924 AN XY: 73944

Gnomad4 AFR AF: 0.0955

Gnomad4 AMR AF: 0.0112

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000209

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000663

Gnomad4 OTH AF: 0.0190

Alfa AF: 0.0119 Hom.: 38

Bravo AF: 0.0313

Asia WGS AF: 0.00550 AC: 19 AN: 3466

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 26, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	6.0
Dann	Benign	0.48

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00011
dbscSNV1_RF	Benign	0.026
SpliceAI score (max)		0.020		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: rs186069439; hg19: chr20-5924683;