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 NM_001372071.1(TRMT112):​c.-146-154G>A variant causes a intron 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 NM_001372071.1 intron
• 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]

PRDX5 (HGNC:9355): (peroxiredoxin 5) This gene encodes a member of the peroxiredoxin family of antioxidant enzymes, which reduce hydrogen peroxide and alkyl hydroperoxides. The encoded protein interacts with peroxisome receptor 1 and plays an antioxidant protective role in different tissues under normal conditions and during inflammatory processes. The use of alternate transcription start sites is thought to result in transcript variants that use different in-frame translational start codons to generate isoforms that are targeted to the mitochondrion (isoform L) or peroxisome/cytoplasm (isoform S). Multiple related pseudogenes have been defined for this gene. [provided by RefSeq, Nov 2017]

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001372071.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRMT112	NM_001372071.1		c.-146-154G>A		intron	N/A	NP_001359000.1	Q9UI30-1
	TRMT112	NM_001372072.1		c.-147+133G>A		intron	N/A	NP_001359001.1	Q9UI30-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRMT112	ENST00000715728.1		c.-300G>A		5_prime_UTR	Exon 1 of 4	ENSP00000520509.1	Q9UI30-1
	TRMT112	ENST00000927039.1		c.-300G>A		5_prime_UTR	Exon 1 of 4	ENSP00000597098.1
	TRMT112	ENST00000905123.1		c.-300G>A		5_prime_UTR	Exon 1 of 4	ENSP00000575182.1

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 v4.9

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;