NM_173084.3:c.1057A>G

Variant names:

• chr3-160438127-T-C
• NM_173084.3:c.1057A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_173084.3(TRIM59):​c.1057A>G​(p.Ile353Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TRIM59 NM_173084.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.886
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05039087).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173084.3. 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	NM_173084.3	MANE Select	c.1057A>G	p.Ile353Val	missense	Exon 3 of 3	NP_775107.1	Q8IWR1-1
	TRIM59-IFT80	NR_148401.1		n.1147+105A>G		intron	N/A
	TRIM59-IFT80	NR_148402.1		n.1077+105A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM59	ENST00000309784.9	TSL:1 MANE Select	c.1057A>G	p.Ile353Val	missense	Exon 3 of 3	ENSP00000311219.4	Q8IWR1-1
	TRIM59-IFT80	ENST00000483754.1	TSL:2	n.952+105A>G		intron	N/A	ENSP00000456272.1	H3BRJ5
	TRIM59	ENST00000870881.1		c.1057A>G	p.Ile353Val	missense	Exon 4 of 4	ENSP00000540940.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	16
DANN	Benign	0.97
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.28
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.35	T
M_CAP	Benign	0.0027	T
MetaRNN	Benign	0.050	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.97	L
PhyloP100		0.89
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.070	N
REVEL	Benign	0.044
Sift	Benign	0.10	T
Sift4G	Benign	0.59	T
Polyphen		0.022	B
Vest4		0.020
MutPred		0.26		Loss of helix (P = 0.0376)
MVP		0.22
MPC		0.052
ClinPred		0.039	T
GERP RS		3.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		0.97
Varity_R		0.021
gMVP		0.060
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

hg19: chr3-160155915;