ENST00000715728.1:c.-300G>C

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 ENST00000715728.1(TRMT112):​c.-300G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000145 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 ENST00000715728.1 5_prime_UTR
• 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRMT112	NM_001372071.1	c.-146-154G>C		intron_variant	Intron 1 of 4		NP_001359000.1
TRMT112	NM_001372072.1	c.-147+133G>C		intron_variant	Intron 1 of 4		NP_001359001.1
TRMT112	XM_047427118.1	c.-281-19G>C		intron_variant	Intron 1 of 4		XP_047283074.1
TRMT112	XM_047427119.1	c.-281-19G>C		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>C		5_prime_UTR_variant	Exon 1 of 4			ENSP00000520509.1

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 v4.3

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;