3-160464269-C-T

Variant names:

• chr3-160464269-C-T
• rs892910
• ENST00000468542.1:c.18+21090G>A

Variant summary

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

The ENST00000468542.1(TRIM59):​c.18+21090G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.976 in 152,194 control chromosomes in the GnomAD database, including 72,457 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 0.98 (72457 hom., 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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.985 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIM59-IFT80	NR_148403.1	n.389+21090G>A		intron_variant	Intron 1 of 20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIM59	ENST00000468542.1	c.18+21090G>A		intron_variant	Intron 1 of 1	4		ENSP00000420451.1

Frequencies

GnomAD3 genomes AF: 0.976 AC: 148386 AN: 152078 Hom.: 72398 Cov.: 30

Gnomad AFR AF: 0.993

Gnomad AMI AF: 0.989

Gnomad AMR AF: 0.972

Gnomad ASJ AF: 0.971

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.992

Gnomad FIN AF: 0.973

Gnomad MID AF: 0.968

Gnomad NFE AF: 0.964

Gnomad OTH AF: 0.959

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

GnomAD4 genome AF: 0.976 AC: 148503 AN: 152194 Hom.: 72457 Cov.: 30 AF XY: 0.977 AC XY: 72727 AN XY: 74412

Gnomad4 AFR AF: 0.993

Gnomad4 AMR AF: 0.972

Gnomad4 ASJ AF: 0.971

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.992

Gnomad4 FIN AF: 0.973

Gnomad4 NFE AF: 0.964

Gnomad4 OTH AF: 0.960

Alfa AF: 0.972 Hom.: 8364

Bravo AF: 0.975

Asia WGS AF: 0.994 AC: 3457 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.15
DANN	Benign	0.75

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;