11-6465613-C-A

Variant names:

• chr11-6465613-C-A
• rs146379181
• NM_033278.4:c.83G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_033278.4(TRIM3):​c.83G>T​(p.Arg28Leu) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R28Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TRIM3 NM_033278.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.75
• Publications: 3 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33235228).

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.83G>T	p.Arg28Leu	missense	Exon 2 of 12	NP_150594.2
	TRIM3	NM_001248006.2		c.83G>T	p.Arg28Leu	missense	Exon 2 of 12	NP_001234935.1	O75382-1
	TRIM3	NM_006458.4		c.83G>T	p.Arg28Leu	missense	Exon 3 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.83G>T	p.Arg28Leu	missense	Exon 2 of 12	ENSP00000340797.3	O75382-1
	TRIM3	ENST00000359518.7	TSL:5	c.83G>T	p.Arg28Leu	missense	Exon 3 of 13	ENSP00000352508.3	O75382-1
	TRIM3	ENST00000525074.5	TSL:2	c.83G>T	p.Arg28Leu	missense	Exon 2 of 12	ENSP00000433102.1	O75382-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Uncertain	0.088	D
BayesDel_noAF	Benign	-0.11
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.27	T
Eigen	Benign	0.12
Eigen_PC	Uncertain	0.22
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.97	D
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-0.32	T
MutationAssessor	Benign	-0.72	N
PhyloP100		2.8
PrimateAI	Uncertain	0.56	T
PROVEAN	Uncertain	-3.1	D
REVEL	Uncertain	0.48
Sift	Uncertain	0.0080	D
Sift4G	Benign	0.10	T
Polyphen		0.99	D
Vest4		0.64
MutPred		0.55		Loss of methylation at K33 (P = 0.0939)
MVP		0.47
MPC		2.2
ClinPred		0.97	D
GERP RS		4.8
Varity_R		0.27
gMVP		0.37
Mutation Taster		=67/33	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs146379181; hg19: chr11-6486843;