rs4680588

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:):

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	UniProt
TRIM59-IFT80	NR_148403.1	n.389+10629A>C		intron_variant, non_coding_transcript_variant

Ensembl

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

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;