11-5611271-ACT-TCA

Variant names:

• chr11-5611271-ACT-TCA
• NM_001003818.3:c.1480_1482delACTinsTCA
• TRIM6 p.Thr494Ser

Variant summary

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

The NM_001003818.3(TRIM6):​c.1480_1482delACTinsTCA​(p.Thr494Ser) variant causes a missense change involving the alteration of a non-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. T494I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TRIM6 NM_001003818.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.371
• Publications: 0 publications found

Genes affected

TRIM6 (HGNC:16277): (tripartite motif containing 6) The protein encoded by this gene is a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains, a RING, B-box type 1 and B-box type 2 domain, and a coiled-coil region. The protein localizes to the nucleus, but its specific function has not been identified. This gene is mapped to chromosome 11p15, where it resides within a TRIM gene cluster. Alternative splicing results in multiple transcript variants. A read-through transcript from this gene into the downstream TRIM34 gene has also been observed, which results in a fusion product from these neighboring family members. [provided by RefSeq, Oct 2010]

TRIM6-TRIM34 (HGNC:33440): (TRIM6-TRIM34 readthrough) The protein encoded by this gene is a member of the tripartite motif (TRIM) family. 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 gene represents a readthrough transcript from genes TRIM6 and TRIM34, and it was described as a splice variant of TRIM34. This gene is mapped to chromosome 11p15, where it resides within a TRIM gene cluster. [provided by RefSeq, Nov 2009]

ENSG00000239920 (HGNC:):

TRIM5 (HGNC:16276): (tripartite motif containing 5) The protein encoded by this gene is a member of the tripartite motif (TRIM) family. 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. The protein forms homo-oligomers via the coilel-coil region and localizes to cytoplasmic bodies. It appears to function as a E3 ubiquitin-ligase and ubiqutinates itself to regulate its subcellular localization. It may play a role in retroviral restriction. Multiple alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Dec 2009]

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001003818.3. 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
	TRIM6	NM_001003818.3	MANE Select	c.1480_1482delACTinsTCA	p.Thr494Ser	missense	N/A	NP_001003818.1	Q9C030-2
	TRIM6	NM_058166.5		c.1396_1398delACTinsTCA	p.Thr466Ser	missense	N/A	NP_477514.1	Q9C030-1
	TRIM6	NM_001198644.2		c.871_873delACTinsTCA	p.Thr291Ser	missense	N/A	NP_001185573.1	Q9C030-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM6	ENST00000380097.8	TSL:1 MANE Select	c.1480_1482delACTinsTCA	p.Thr494Ser	missense	N/A	ENSP00000369440.3	Q9C030-2
	TRIM6	ENST00000278302.9	TSL:1	c.1396_1398delACTinsTCA	p.Thr466Ser	missense	N/A	ENSP00000278302.5	Q9C030-1
	TRIM6	ENST00000380107.5	TSL:1	c.1318_1320delACTinsTCA	p.Thr440Ser	missense	N/A	ENSP00000369450.1	E9PFM0

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		0.37

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: chr11-5632501;