11-6456831-C-T

Position:

• chr11-6456831-C-T

Variant summary

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

The NM_033278.4(TRIM3):​c.895G>A​(p.Val299Ile) 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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TRIM3 NM_033278.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.222

Genes affected

TRIM3 (HGNC:10064): (tripartite motif containing 3) The protein encoded by this gene is a member of the tripartite motif (TRIM) family, also called the 'RING-B-box-coiled-coil' (RBCC) subgroup of RING finger proteins. 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. This protein localizes to cytoplasmic filaments. It is similar to a rat protein which is a specific partner for the tail domain of myosin V, a class of myosins which are involved in the targeted transport of organelles. The rat protein can also interact with alpha-actinin-4. Thus it is suggested that this human protein may play a role in myosin V-mediated cargo transport. Alternatively spliced transcript variants encoding the same isoform have been identified. [provided by RefSeq, Jul 2008]

TRIM3 (HGNC:):

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=0.08156702).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM3	NM_033278.4	c.895G>A	p.Val299Ile	missense_variant	6/12	ENST00000345851.8	NP_150594.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM3	ENST00000345851.8	c.895G>A	p.Val299Ile	missense_variant	6/12	1	NM_033278.4	ENSP00000340797.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000404 AC: 1 AN: 247374 Hom.: 0 AF XY: 0.00000743 AC XY: 1 AN XY: 134508

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000898

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

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

Oct 01, 2024

The c.895G>A (p.V299I) alteration is located in exon 7 (coding exon 5) of the TRIM3 gene. This alteration results from a G to A substitution at nucleotide position 895, causing the valine (V) at amino acid position 299 to be replaced by an isoleucine (I). 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	0.090
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	17
DANN	Benign	0.90
DEOGEN2	Benign	0.12	T;T;.;T;.
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.45
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.84	.;.;T;T;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.082	T;T;T;T;T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	0.090	N;N;.;N;.
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-0.18	N;N;N;N;.
REVEL	Benign	0.078
Sift	Benign	0.87	T;T;T;T;.
Sift4G	Benign	0.62	T;T;T;T;.
Polyphen		0.0	B;B;.;B;.
Vest4		0.055
MutPred		0.29		Loss of disorder (P = 0.1067);Loss of disorder (P = 0.1067);.;Loss of disorder (P = 0.1067);.;
MVP		0.13
MPC		0.85
ClinPred		0.055	T
GERP RS		3.3
Varity_R		0.022
gMVP		0.37

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: rs1292309680; hg19: chr11-6478061;