3-160464269-C-A

Position:

• chr3-160464269-C-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000468542.1(TRIM59):​c.18+21090G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 30)
• Consequence: TRIM59 ENST00000468542.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.55

Genes affected

TRIM59 (HGNC:30834): (tripartite motif containing 59) Predicted to enable ubiquitin protein ligase activity. Acts upstream of or within negative regulation of I-kappaB kinase/NF-kappaB signaling. Predicted to be located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

TRIM59-IFT80 (HGNC:56756): (TRIM59-IFT80 readthrough (NMD candidate)) This locus represents naturally occurring readthrough transcription between the neighboring TRIM59 (tripartite motif containing 59) and IFT80 (intraflagellar transport 80) genes on chromosome 3. The readthrough transcript is unlikely to produce a protein product. [provided by RefSeq, Jun 2017]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM59-IFT80	NR_148403.1	n.389+21090G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM59	ENST00000468542.1	c.18+21090G>T		intron_variant		4		ENSP00000420451.1

Frequencies

GnomAD3 genomes Cov.: 30

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.11
DANN	Benign	0.71

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs892910; hg19: chr3-160182057;