11-64317826-C-T

Variant names:

• chr11-64317826-C-T
• rs9787810
• ENST00000715728.1:c.-300G>A

Variant summary

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

The ENST00000715728.1(TRMT112):​c.-300G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.286 in 840,752 control chromosomes in the GnomAD database, including 37,668 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 0.22 (4831 hom., cov: 34)
  • Exomes 𝑓: 0.30 (32837 hom.)
• Consequence: TRMT112 ENST00000715728.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.27
• Publications: 23 publications found

Genes affected

TRMT112 (HGNC:26940): (tRNA methyltransferase activator subunit 11-2) Enables protein heterodimerization activity and protein methyltransferase activity. Involved in macromolecule methylation and positive regulation of rRNA processing. Located in nucleoplasm and perinuclear region of cytoplasm. Part of protein-containing complex. [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=-0.73).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.319 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRMT112	NM_001372071.1	c.-146-154G>A		intron_variant	Intron 1 of 4		NP_001359000.1
TRMT112	NM_001372072.1	c.-147+133G>A		intron_variant	Intron 1 of 4		NP_001359001.1
TRMT112	XM_047427118.1	c.-281-19G>A		intron_variant	Intron 1 of 4		XP_047283074.1
TRMT112	XM_047427119.1	c.-281-19G>A		intron_variant	Intron 1 of 4		XP_047283075.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRMT112	ENST00000715728.1	c.-300G>A		5_prime_UTR_variant	Exon 1 of 4			ENSP00000520509.1

Frequencies

GnomAD3 genomes AF: 0.225 AC: 34210 AN: 152068 Hom.: 4833 Cov.: 34

Gnomad AFR AF: 0.0686

Gnomad AMI AF: 0.367

Gnomad AMR AF: 0.182

Gnomad ASJ AF: 0.276

Gnomad EAS AF: 0.0890

Gnomad SAS AF: 0.303

Gnomad FIN AF: 0.265

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.323

Gnomad OTH AF: 0.251

GnomAD4 exome AF: 0.299 AC: 206081 AN: 688566 Hom.: 32837 Cov.: 9 AF XY: 0.302 AC XY: 103579 AN XY: 343248

African (AFR) AF: 0.0581 AC: 915 AN: 15754

American (AMR) AF: 0.155 AC: 1902 AN: 12272

Ashkenazi Jewish (ASJ) AF: 0.283 AC: 3984 AN: 14074

East Asian (EAS) AF: 0.0853 AC: 2297 AN: 26934

South Asian (SAS) AF: 0.318 AC: 12462 AN: 39218

European-Finnish (FIN) AF: 0.265 AC: 7089 AN: 26792

Middle Eastern (MID) AF: 0.327 AC: 766 AN: 2344

European-Non Finnish (NFE) AF: 0.323 AC: 167659 AN: 518564

Other (OTH) AF: 0.276 AC: 9007 AN: 32614

GnomAD4 genome AF: 0.225 AC: 34201 AN: 152186 Hom.: 4831 Cov.: 34 AF XY: 0.224 AC XY: 16671 AN XY: 74398

African (AFR) AF: 0.0685 AC: 2846 AN: 41538

American (AMR) AF: 0.181 AC: 2769 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.276 AC: 956 AN: 3470

East Asian (EAS) AF: 0.0890 AC: 461 AN: 5180

South Asian (SAS) AF: 0.303 AC: 1460 AN: 4826

European-Finnish (FIN) AF: 0.265 AC: 2805 AN: 10574

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.323 AC: 21966 AN: 68000

Other (OTH) AF: 0.248 AC: 522 AN: 2108

Alfa AF: 0.295 Hom.: 4645

Bravo AF: 0.210

Asia WGS AF: 0.168 AC: 584 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	4.9
DANN	Benign	0.77
PhyloP100		-1.3
PromoterAI		0.0080	Neutral
Mutation Taster		=300/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs9787810; hg19: chr11-64085298;