rs4680588

Variant names:

• chr3-160474730-T-G
• rs4680588
• ENST00000468542.1:c.18+10629A>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TRIM59-IFT80	NR_148403.1	n.389+10629A>C		intron_variant	Intron 1 of 20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIM59	ENST00000468542.1	c.18+10629A>C		intron_variant	Intron 1 of 1	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

African (AFR) AF: 0.573 AC: 23703 AN: 41400

American (AMR) AF: 0.444 AC: 6779 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.445 AC: 1543 AN: 3468

East Asian (EAS) AF: 0.254 AC: 1305 AN: 5132

South Asian (SAS) AF: 0.400 AC: 1921 AN: 4800

European-Finnish (FIN) AF: 0.616 AC: 6489 AN: 10528

Middle Eastern (MID) AF: 0.415 AC: 122 AN: 294

European-Non Finnish (NFE) AF: 0.542 AC: 36818 AN: 67930

Other (OTH) AF: 0.489 AC: 1028 AN: 2104

Alfa AF: 0.527 Hom.: 64819

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
PhyloP100		-0.75

Splicing

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

Other links and lift over

dbSNP: rs4680588; hg19: chr3-160192518;