11-6457014-G-C

Variant names:

• chr11-6457014-G-C
• rs955022236
• NM_033278.4:c.712C>G

Variant summary

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

The NM_033278.4(TRIM3):​c.712C>G​(p.Leu238Val) 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. 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: Not reported in ClinVar
• Conservation: PhyloP100: 1.99

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]

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=0.16765895).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIM3	NM_033278.4	c.712C>G	p.Leu238Val	missense_variant	Exon 6 of 12	ENST00000345851.8	NP_150594.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIM3	ENST00000345851.8	c.712C>G	p.Leu238Val	missense_variant	Exon 6 of 12	1	NM_033278.4	ENSP00000340797.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.00048	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	9.5
DANN	Benign	0.85
DEOGEN2	Benign	0.15	T;T;.;T;.;T
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.45
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	.;.;D;D;D;D
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.17	T;T;T;T;T;T
MetaSVM	Benign	-0.68	T
MutationAssessor	Benign	1.5	L;L;.;L;.;.
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-0.40	N;N;N;N;.;N
REVEL	Benign	0.10
Sift	Benign	0.28	T;T;T;T;.;T
Sift4G	Benign	0.46	T;T;T;T;.;.
Polyphen		0.058	B;B;.;B;.;.
Vest4		0.60
MutPred		0.35		Loss of helix (P = 0.0376);Loss of helix (P = 0.0376);.;Loss of helix (P = 0.0376);.;Loss of helix (P = 0.0376);
MVP		0.41
MPC		2.2
ClinPred		0.25	T
GERP RS		-0.12
Varity_R		0.071
gMVP		0.35

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: rs955022236; hg19: chr11-6478244;