3-160464269-C-T

Variant names:

• chr3-160464269-C-T
• rs892910
• ENST00000870881.1:c.-254-14617G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.985 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000468542.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM59-IFT80	NR_148403.1		n.389+21090G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM59	ENST00000870881.1		c.-254-14617G>A		intron	N/A	ENSP00000540940.1
	TRIM59	ENST00000468542.1	TSL:4	c.18+21090G>A		intron	N/A	ENSP00000420451.1	C9JNB9

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

African (AFR) AF: 0.993 AC: 41259 AN: 41542

American (AMR) AF: 0.972 AC: 14877 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.971 AC: 3370 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5184 AN: 5184

South Asian (SAS) AF: 0.992 AC: 4777 AN: 4816

European-Finnish (FIN) AF: 0.973 AC: 10270 AN: 10560

Middle Eastern (MID) AF: 0.966 AC: 284 AN: 294

European-Non Finnish (NFE) AF: 0.964 AC: 65558 AN: 68010

Other (OTH) AF: 0.960 AC: 2022 AN: 2106

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.15
DANN	Benign	0.75
PhyloP100		-1.6

Splicing

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

Other links and lift over

dbSNP: rs892910; hg19: chr3-160182057;