11-6465613-CG-AA

Variant names:

• chr11-6465613-CG-AA
• NM_033278.4:c.82_83delCGinsTT
• TRIM3 p.Arg28Leu

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_033278.4(TRIM3):​c.82_83delCGinsTT​(p.Arg28Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. 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: 9.98
• 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 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

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.82_83delCGinsTT	p.Arg28Leu	missense	N/A	NP_150594.2
	TRIM3	NM_001248006.2		c.82_83delCGinsTT	p.Arg28Leu	missense	N/A	NP_001234935.1	O75382-1
	TRIM3	NM_006458.4		c.82_83delCGinsTT	p.Arg28Leu	missense	N/A	NP_006449.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM3	ENST00000345851.8	TSL:1 MANE Select	c.82_83delCGinsTT	p.Arg28Leu	missense	N/A	ENSP00000340797.3	O75382-1
	TRIM3	ENST00000359518.7	TSL:5	c.82_83delCGinsTT	p.Arg28Leu	missense	N/A	ENSP00000352508.3	O75382-1
	TRIM3	ENST00000525074.5	TSL:2	c.82_83delCGinsTT	p.Arg28Leu	missense	N/A	ENSP00000433102.1	O75382-1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		10

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr11-6486843;