chr3-160438027-A-G

Position:

• chr3-160438027-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_173084.3(TRIM59):​c.1157T>C​(p.Leu386Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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: 5.93

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]

ENSG00000248710 (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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM59	NM_173084.3	c.1157T>C	p.Leu386Pro	missense_variant	3/3	ENST00000309784.9	NP_775107.1
TRIM59-IFT80	NR_148401.1	n.1147+205T>C		intron_variant
TRIM59-IFT80	NR_148402.1	n.1077+205T>C		intron_variant
TRIM59-IFT80	NR_148403.1	n.1344+205T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM59	ENST00000309784.9	c.1157T>C	p.Leu386Pro	missense_variant	3/3	1	NM_173084.3	ENSP00000311219.4
ENSG00000248710	ENST00000483754.1	n.952+205T>C		intron_variant		2		ENSP00000456272.1
TRIM59	ENST00000543469.1	c.952+205T>C		intron_variant		5		ENSP00000444313.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 05, 2022

The c.1157T>C (p.L386P) alteration is located in exon 3 (coding exon 1) of the TRIM59 gene. This alteration results from a T to C substitution at nucleotide position 1157, causing the leucine (L) at amino acid position 386 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Pathogenic	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.019	T
Eigen	Benign	0.0094
Eigen_PC	Benign	-0.056
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.31	T
M_CAP	Benign	0.036	D
MetaRNN	Uncertain	0.55	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.97	L
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.93	N
REVEL	Benign	0.26
Sift	Uncertain	0.013	D
Sift4G	Benign	0.22	T
Polyphen		0.95	P
Vest4		0.66
MutPred		0.47		Gain of loop (P = 0.0195);
MVP		0.49
MPC		0.37
ClinPred		0.59	D
GERP RS		5.7
Varity_R		0.50
gMVP		0.66

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-160155815;