Variant 20-5944037-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_015939.5(TRMT6):c.459-6C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00543 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, intron

Scores

Splicing: ADA: 0.0001074

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0400

Variant links:

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 links:

TRMT6 (HGNC:):

TRMT6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 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_multiple_submitters_no_conflicts, 2 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	Protein	UniProt
TRMT6	NM_015939.5 linkuse as main transcript	c.459-6C>T		splice_region_variant, intron_variant		ENST00000203001.7	NP_057023.2	Q9UJA5-1
TRMT6	NM_001281467.2 linkuse as main transcript	c.-52-6C>T		splice_region_variant, intron_variant			NP_001268396.1	Q9UJA5-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRMT6	ENST00000203001.7 linkuse as main transcript	c.459-6C>T		splice_region_variant, intron_variant		1	NM_015939.5	ENSP00000203001.2		Q9UJA5-1

Frequencies

GnomAD3 genomes

AF:

0.0276

AC:

4178

AN:

151210

Hom.:

185

Cov.:

show subpopulations

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.:

AF XY:

0.00570

AC XY:

718

AN XY:

125992

show subpopulations

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.:

AF XY:

0.00271

AC XY:

1905

AN XY:

702548

show subpopulations

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.:

AF XY:

0.0260

AC XY:

1924

AN XY:

73944

show subpopulations

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.:

Bravo

AF:

0.0313

Asia WGS

AF:

0.00550

AC:

AN:

3466

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 26, 2018	- -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over