chr6-30168318-A-G

Position:

• chr6-30168318-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_033229.3(TRIM15):​c.496A>G​(p.Lys166Glu) 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. 14/21 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: TRIM15 NM_033229.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.483

Genes affected

TRIM15 (HGNC:16284): (tripartite motif containing 15) The protein encoded by this gene is a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. The protein localizes to the cytoplasm. Alternatively spliced transcript variants have been described, but their biological validity has not been determined. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13170156).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIM15	NM_033229.3	c.496A>G	p.Lys166Glu	missense_variant	3/7	ENST00000376694.9
TRIM15	XM_011514987.2	c.181A>G	p.Lys61Glu	missense_variant	4/8
TRIM15	XM_047419503.1	c.496A>G	p.Lys166Glu	missense_variant	3/5
TRIM15	XM_011514988.3			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIM15	ENST00000376694.9	c.496A>G	p.Lys166Glu	missense_variant	3/7	1	NM_033229.3	P1
TRIM15	ENST00000619857.4	c.289A>G	p.Lys97Glu	missense_variant	3/8	5
TRIM15	ENST00000433744.1	c.7A>G	p.Lys3Glu	missense_variant	1/5	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

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

Sep 16, 2021

The c.496A>G (p.K166E) alteration is located in exon 3 (coding exon 3) of the TRIM15 gene. This alteration results from a A to G substitution at nucleotide position 496, causing the lysine (K) at amino acid position 166 to be replaced by a glutamic acid (E). 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	0.28
BayesDel_addAF	Benign	-0.053	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.032	T;T
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.21
FATHMM_MKL	Benign	0.49	N
M_CAP	Benign	0.072	D
MetaRNN	Benign	0.13	T;T
MetaSVM	Benign	-0.88	T
MutationAssessor	Uncertain	2.8	.;M
MutationTaster	Benign	1.0	D;N
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-2.3	.;N
REVEL	Benign	0.21
Sift	Benign	0.093	.;T
Sift4G	Uncertain	0.0090	D;D
Polyphen		0.89	.;P
Vest4		0.11
MutPred		0.43		.;Loss of ubiquitination at K166 (P = 0.0041);
MVP		0.81
MPC		0.59
ClinPred		0.71	D
GERP RS		2.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.078
gMVP		0.20

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr6-30136095;