6-30163951-G-T

Position:

• chr6-30163951-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_033229.3(TRIM15):​c.267G>T​(p.Lys89Asn) 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. 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: -0.0350

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]

TRIM10 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32819676).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM15	NM_033229.3	c.267G>T	p.Lys89Asn	missense_variant	1/7	ENST00000376694.9	NP_150232.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM15	ENST00000376694.9	c.267G>T	p.Lys89Asn	missense_variant	1/7	1	NM_033229.3	ENSP00000365884	P1
TRIM15	ENST00000619857.4	c.60G>T	p.Lys20Asn	missense_variant	1/8	5		ENSP00000484001

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

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

Feb 15, 2023

The c.267G>T (p.K89N) alteration is located in exon 1 (coding exon 1) of the TRIM15 gene. This alteration results from a G to T substitution at nucleotide position 267, causing the lysine (K) at amino acid position 89 to be replaced by an asparagine (N). 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	Pathogenic	0.72
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.070	T;T;.
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Benign	0.44	N
LIST_S2	Benign	0.79	.;.;T
M_CAP	Benign	0.055	D
MetaRNN	Benign	0.33	T;T;T
MetaSVM	Benign	-0.57	T
MutationAssessor	Pathogenic	3.1	.;M;M
MutationTaster	Benign	0.95	N;N
PrimateAI	Uncertain	0.71	T
PROVEAN	Uncertain	-3.0	.;D;D
REVEL	Benign	0.18
Sift	Uncertain	0.0020	.;D;D
Sift4G	Uncertain	0.013	D;D;D
Polyphen		1.0	.;D;.
Vest4		0.19
MutPred		0.52		.;Loss of methylation at K89 (P = 0.01);Loss of methylation at K89 (P = 0.01);
MVP		0.74
MPC		1.3
ClinPred		0.98	D
GERP RS		4.6
Varity_R		0.69
gMVP		0.25

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

LitVar

Other links and lift over

dbSNP: rs747110315; hg19: chr6-30131728;