Variant rs10485494 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000203001.7(TRMT6):c.1303-6G>C 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 0.0452 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
ENST00000203001.7 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0001885

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.519

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRMT6	NM_015939.5 linkuse as main transcript	c.1303-6G>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000203001.7	NP_057023.2
TRMT6	NM_001281467.2 linkuse as main transcript	c.793-6G>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			NP_001268396.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
TRMT6	ENST00000203001.7 linkuse as main transcript	c.1303-6G>C	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	1	NM_015939.5	ENSP00000203001	P1	Q9UJA5-1
TRMT6	ENST00000453074.6 linkuse as main transcript	c.793-6G>C	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	2		ENSP00000392070		Q9UJA5-4
TRMT6	ENST00000466974.5 linkuse as main transcript	n.2083-6G>C	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant	2
TRMT6	ENST00000473131.5 linkuse as main transcript	n.1534-6G>C	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant	5

Frequencies

GnomAD3 genomes

AF:

0.0499

AC:

7587

AN:

152168

Hom.:

206

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.0415

AC:

10391

AN:

250268

Hom.:

292

AF XY:

0.0420

AC XY:

5676

AN XY:

135256

show subpopulations

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 SAS exome

AF:

0.0208

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.:

AF XY:

0.0444

AC XY:

32262

AN XY:

726562

show subpopulations

Gnomad4 AFR exome

AF:

0.0677

Gnomad4 AMR exome

AF:

0.0350

Gnomad4 ASJ exome

AF:

0.0649

Gnomad4 EAS exome

AF:

0.00691

Gnomad4 SAS exome

AF:

0.0221

Gnomad4 FIN exome

AF:

0.0271

Gnomad4 NFE exome

AF:

0.0477

Gnomad4 OTH exome

AF:

0.0470

GnomAD4 genome

AF:

0.0499

AC:

7600

AN:

152286

Hom.:

206

Cov.:

AF XY:

0.0492

AC XY:

3661

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.0656

Gnomad4 AMR

AF:

0.0462

Gnomad4 ASJ

AF:

0.0726

Gnomad4 EAS

AF:

0.00732

Gnomad4 SAS

AF:

0.0228

Gnomad4 FIN

AF:

0.0314

Gnomad4 NFE

AF:

0.0471

Gnomad4 OTH

AF:

0.0657

Alfa

AF:

0.0508

Hom.:

Bravo

AF:

0.0525

Asia WGS

AF:

0.0200

AC:

AN:

3478

EpiCase

AF:

0.0558

EpiControl

AF:

0.0592

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

6.5

DANN

Benign

0.72

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over