rs6935937

chr6-126170164-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000648977.1(TRMT11):c.*1824-4661T>C variant causes a intron, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.331 in 151,926 control chromosomes in the GnomAD database, including 8,927 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 0.33 (8927 hom., cov: 32)
• Consequence: TRMT11 ENST00000648977.1 intron, NMD_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.31

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.435 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRMT11	XR_007059289.1	n.1778-4661T>C		intron_variant, non_coding_transcript_variant
TRMT11	XR_007059290.1	n.2031-4661T>C		intron_variant, non_coding_transcript_variant
TRMT11	XR_007059291.1	n.1493-4661T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRMT11	ENST00000648977.1	c.*1824-4661T>C		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.331 AC: 50254 AN: 151808 Hom.: 8905 Cov.: 32

Gnomad AFR AF: 0.441

Gnomad AMI AF: 0.147

Gnomad AMR AF: 0.251

Gnomad ASJ AF: 0.277

Gnomad EAS AF: 0.0195

Gnomad SAS AF: 0.271

Gnomad FIN AF: 0.273

Gnomad MID AF: 0.207

Gnomad NFE AF: 0.326

Gnomad OTH AF: 0.310

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

GnomAD4 genome AF: 0.331 AC: 50324 AN: 151926 Hom.: 8927 Cov.: 32 AF XY: 0.323 AC XY: 23990 AN XY: 74254

Gnomad4 AFR AF: 0.441

Gnomad4 AMR AF: 0.251

Gnomad4 ASJ AF: 0.277

Gnomad4 EAS AF: 0.0193

Gnomad4 SAS AF: 0.272

Gnomad4 FIN AF: 0.273

Gnomad4 NFE AF: 0.326

Gnomad4 OTH AF: 0.313

Alfa AF: 0.319 Hom.: 10937

Bravo AF: 0.331

Asia WGS AF: 0.209 AC: 723 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	13
Dann	Benign	0.83

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs6935937; hg19: chr6-126491310;