chr16-88706480-C-A

Variant names:

• chr16-88706480-C-A
• rs1910828521
• NM_001012759.3:c.-51C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001012759.3(CTU2):​c.-51C>A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000085 in 1,176,746 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: 33)
  • Exomes 𝑓: 8.5e-7 (0 hom.)
• Consequence: CTU2 NM_001012759.3 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.658
• Publications: 0 publications found

Genes affected

CTU2 (HGNC:28005): (cytosolic thiouridylase subunit 2) This gene encodes a protein which is involved in the post-transcriptional modification of transfer RNAs (tRNAs). The encoded protein plays a role in thiolation of uridine residue present at the wobble position in a subset of tRNAs, resulting in enhanced codon reading accuracy. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jan 2016]

RNF166 (HGNC:28856): (ring finger protein 166) Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in protein polyubiquitination and ubiquitin-dependent protein catabolic process. Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTU2	NM_001012759.3	c.-51C>A		upstream_gene_variant		ENST00000453996.7	NP_001012777.1
RNF166	NM_178841.4	c.-155G>T		upstream_gene_variant		ENST00000312838.9	NP_849163.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTU2	ENST00000453996.7	c.-51C>A		upstream_gene_variant		1	NM_001012759.3	ENSP00000388320.2
RNF166	ENST00000312838.9	c.-155G>T		upstream_gene_variant		1	NM_178841.4	ENSP00000326095.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 8.50e-7 AC: 1 AN: 1176746 Hom.: 0 Cov.: 24 AF XY: 0.00000175 AC XY: 1 AN XY: 571476

⚠️ 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: 23004

American (AMR) AF: 0.00 AC: 0 AN: 9414

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16378

East Asian (EAS) AF: 0.00 AC: 0 AN: 26692

South Asian (SAS) AF: 0.0000205 AC: 1 AN: 48840

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28666

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3366

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 972278

Other (OTH) AF: 0.00 AC: 0 AN: 48108

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
CADD	Benign	5.1
DANN	Benign	0.87
PhyloP100		-0.66
PromoterAI		-0.020	Neutral

Splicing

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

Other links and lift over

dbSNP: rs1910828521; hg19: chr16-88772888;