11-64317826-C-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001372071.1(TRMT112):​c.-146-154G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000145 in 690,228 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 34)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: TRMT112 NM_001372071.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.27
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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>C		intron	N/A	NP_001359000.1	Q9UI30-1
	TRMT112	NM_001372072.1		c.-147+133G>C		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>C		5_prime_UTR	Exon 1 of 4	ENSP00000520509.1	Q9UI30-1
	TRMT112	ENST00000927039.1		c.-300G>C		5_prime_UTR	Exon 1 of 4	ENSP00000597098.1
	TRMT112	ENST00000905123.1		c.-300G>C		5_prime_UTR	Exon 1 of 4	ENSP00000575182.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000145 AC: 1 AN: 690228 Hom.: 0 Cov.: 9 AF XY: 0.00000291 AC XY: 1 AN XY: 344114

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 15764

American (AMR) AF: 0.00 AC: 0 AN: 12292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14102

East Asian (EAS) AF: 0.00 AC: 0 AN: 26946

South Asian (SAS) AF: 0.00 AC: 0 AN: 39296

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 26850

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2348

European-Non Finnish (NFE) AF: 0.00000192 AC: 1 AN: 519944

Other (OTH) AF: 0.00 AC: 0 AN: 32686

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	3.4
DANN	Benign	0.59
PhyloP100		-1.3
PromoterAI		0.0092	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.22		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.22		Position offset: -3

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

Other links and lift over

dbSNP: rs9787810; hg19: chr11-64085298;