chr11-6457442-C-G

Variant names:

• chr11-6457442-C-G
• rs777600054
• NM_033278.4:c.550G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_033278.4(TRIM3):​c.550G>C​(p.Gly184Arg) 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. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TRIM3 NM_033278.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.53
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09262276).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033278.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM3	NM_033278.4	MANE Select	c.550G>C	p.Gly184Arg	missense	Exon 5 of 12	NP_150594.2
	TRIM3	NM_001248006.2		c.550G>C	p.Gly184Arg	missense	Exon 5 of 12	NP_001234935.1	O75382-1
	TRIM3	NM_006458.4		c.550G>C	p.Gly184Arg	missense	Exon 6 of 13	NP_006449.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM3	ENST00000345851.8	TSL:1 MANE Select	c.550G>C	p.Gly184Arg	missense	Exon 5 of 12	ENSP00000340797.3	O75382-1
	TRIM3	ENST00000359518.7	TSL:5	c.550G>C	p.Gly184Arg	missense	Exon 6 of 13	ENSP00000352508.3	O75382-1
	TRIM3	ENST00000525074.5	TSL:2	c.550G>C	p.Gly184Arg	missense	Exon 5 of 12	ENSP00000433102.1	O75382-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.023	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	22
DANN	Benign	0.90
DEOGEN2	Benign	0.075	T
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.14
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.050	D
MetaRNN	Benign	0.093	T
MetaSVM	Benign	-0.57	T
MutationAssessor	Benign	0.20	N
PhyloP100		1.5
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	0.50	N
REVEL	Benign	0.079
Sift	Benign	0.39	T
Sift4G	Benign	0.39	T
Polyphen		0.010	B
Vest4		0.39
MutPred		0.38		Gain of MoRF binding (P = 0.0026)
MVP		0.16
MPC		0.022
ClinPred		0.22	T
GERP RS		5.2
Varity_R		0.070
gMVP		0.37
Mutation Taster		=85/15	polymorphism

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

Other links and lift over

dbSNP: rs777600054; hg19: chr11-6478672;