rs4680588

Positions:

• chr3-160474730-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000468542.1(TRIM59):​c.18+10629A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.529 in 151,850 control chromosomes in the GnomAD database, including 21,742 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 0.53 (21742 hom., cov: 31)
• Consequence: TRIM59 ENST00000468542.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.754

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.566 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM59-IFT80	NR_148403.1	n.389+10629A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM59	ENST00000468542.1	c.18+10629A>C		intron_variant		4		ENSP00000420451.1

Frequencies

GnomAD3 genomes AF: 0.529 AC: 80262 AN: 151732 Hom.: 21700 Cov.: 31

Gnomad AFR AF: 0.572

Gnomad AMI AF: 0.723

Gnomad AMR AF: 0.444

Gnomad ASJ AF: 0.445

Gnomad EAS AF: 0.254

Gnomad SAS AF: 0.400

Gnomad FIN AF: 0.616

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.542

Gnomad OTH AF: 0.483

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

GnomAD4 genome AF: 0.529 AC: 80367 AN: 151850 Hom.: 21742 Cov.: 31 AF XY: 0.526 AC XY: 39021 AN XY: 74192

Gnomad4 AFR AF: 0.573

Gnomad4 AMR AF: 0.444

Gnomad4 ASJ AF: 0.445

Gnomad4 EAS AF: 0.254

Gnomad4 SAS AF: 0.400

Gnomad4 FIN AF: 0.616

Gnomad4 NFE AF: 0.542

Gnomad4 OTH AF: 0.489

Alfa AF: 0.522 Hom.: 40751

Bravo AF: 0.520

Asia WGS AF: 0.385 AC: 1342 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.44
DANN	Benign	0.37

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4680588; hg19: chr3-160192518;