6-126033128-A-T

Variant names:

• chr6-126033128-A-T
• rs941458
• NM_001031712.3:c.1261-5577A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001031712.3(TRMT11):​c.1261-5577A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.578 in 151,972 control chromosomes in the GnomAD database, including 26,950 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 0.58 (26950 hom., cov: 32)
• Consequence: TRMT11 NM_001031712.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.652
• Publications: 5 publications found

Genes affected

TRMT11 (HGNC:21080): (tRNA methyltransferase 11 homolog) Predicted to enable tRNA (guanine-N2-)-methyltransferase activity. Predicted to be involved in tRNA methylation. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.899 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRMT11	NM_001031712.3	c.1261-5577A>T		intron_variant	Intron 12 of 12	ENST00000334379.11	NP_001026882.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRMT11	ENST00000334379.11	c.1261-5577A>T		intron_variant	Intron 12 of 12	1	NM_001031712.3	ENSP00000333934.5
TRMT11	ENST00000466316.1	n.*667-5577A>T		intron_variant	Intron 6 of 6	5		ENSP00000466001.3

Frequencies

GnomAD3 genomes AF: 0.577 AC: 87643 AN: 151854 Hom.: 26894 Cov.: 32

Gnomad AFR AF: 0.735

Gnomad AMI AF: 0.239

Gnomad AMR AF: 0.636

Gnomad ASJ AF: 0.430

Gnomad EAS AF: 0.920

Gnomad SAS AF: 0.615

Gnomad FIN AF: 0.581

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.452

Gnomad OTH AF: 0.545

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.578 AC: 87766 AN: 151972 Hom.: 26950 Cov.: 32 AF XY: 0.586 AC XY: 43543 AN XY: 74288

African (AFR) AF: 0.735 AC: 30479 AN: 41456

American (AMR) AF: 0.637 AC: 9724 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.430 AC: 1491 AN: 3470

East Asian (EAS) AF: 0.920 AC: 4760 AN: 5172

South Asian (SAS) AF: 0.615 AC: 2961 AN: 4814

European-Finnish (FIN) AF: 0.581 AC: 6136 AN: 10554

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.452 AC: 30693 AN: 67924

Other (OTH) AF: 0.549 AC: 1157 AN: 2106

Alfa AF: 0.521 Hom.: 2695

Bravo AF: 0.591

Asia WGS AF: 0.748 AC: 2595 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.32
DANN	Benign	0.66
PhyloP100		-0.65
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs941458; hg19: chr6-126354274;