20-5950269-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_015939.5(TRMT6):c.128+9G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00669 in 1,597,026 control chromosomes in the GnomAD database, including 60 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0055 (6 hom., cov: 32)
  • Exomes 𝑓: 0.0068 (54 hom.)
• Consequence: TRMT6 NM_015939.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.118

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=-0.75).
• BP6: Variant 20-5950269-C-G is Benign according to our data. Variant chr20-5950269-C-G is described in ClinVar as [Benign]. Clinvar id is 770666.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.00681 (9841/1444706) while in subpopulation AMR AF= 0.021 (921/43916). AF 95% confidence interval is 0.0198. There are 54 homozygotes in gnomad4_exome. There are 4756 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRMT6	NM_015939.5	c.128+9G>C		intron_variant		ENST00000203001.7
TRMT6	NM_001281467.2	c.-273+9G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRMT6	ENST00000203001.7	c.128+9G>C		intron_variant		1	NM_015939.5	P1

Frequencies

GnomAD3 genomes AF: 0.00553 AC: 841 AN: 152202 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.00130

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0101

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00186

Gnomad FIN AF: 0.0121

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00708

Gnomad OTH AF: 0.00382

GnomAD3 exomes AF: 0.00780 AC: 1891 AN: 242402 Hom.: 19 AF XY: 0.00715 AC XY: 940 AN XY: 131464

Gnomad AFR exome AF: 0.00120

Gnomad AMR exome AF: 0.0228

Gnomad ASJ exome AF: 0.00112

Gnomad EAS exome AF: 0.000115

Gnomad SAS exome AF: 0.00253

Gnomad FIN exome AF: 0.0117

Gnomad NFE exome AF: 0.00665

Gnomad OTH exome AF: 0.00853

GnomAD4 exome AF: 0.00681 AC: 9841 AN: 1444706 Hom.: 54 Cov.: 31 AF XY: 0.00664 AC XY: 4756 AN XY: 716558

Gnomad4 AFR exome AF: 0.000761

Gnomad4 AMR exome AF: 0.0210

Gnomad4 ASJ exome AF: 0.00159

Gnomad4 EAS exome AF: 0.000182

Gnomad4 SAS exome AF: 0.00221

Gnomad4 FIN exome AF: 0.0130

Gnomad4 NFE exome AF: 0.00697

Gnomad4 OTH exome AF: 0.00500

GnomAD4 genome AF: 0.00551 AC: 839 AN: 152320 Hom.: 6 Cov.: 32 AF XY: 0.00575 AC XY: 428 AN XY: 74476

Gnomad4 AFR AF: 0.00130

Gnomad4 AMR AF: 0.00993

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00186

Gnomad4 FIN AF: 0.0121

Gnomad4 NFE AF: 0.00709

Gnomad4 OTH AF: 0.00378

Alfa AF: 0.00646 Hom.: 1

Bravo AF: 0.00527

Asia WGS AF: 0.00260 AC: 9 AN: 3478

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

May 25, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
Cadd	Benign	5.9
Dann	Benign	0.70

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: rs41282140; hg19: chr20-5930915;