chr11-5611272-C-G

Variant names:

• chr11-5611272-C-G
• rs145524814
• NM_001003818.3:c.1481C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001003818.3(TRIM6):​c.1481C>G​(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. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. 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: 0.0980
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.039401412).

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.1481C>G	p.Thr494Ser	missense	Exon 8 of 8	NP_001003818.1	Q9C030-2
	TRIM6	NM_058166.5		c.1397C>G	p.Thr466Ser	missense	Exon 8 of 8	NP_477514.1	Q9C030-1
	TRIM6	NM_001198644.2		c.872C>G	p.Thr291Ser	missense	Exon 7 of 7	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.1481C>G	p.Thr494Ser	missense	Exon 8 of 8	ENSP00000369440.3	Q9C030-2
	TRIM6	ENST00000278302.9	TSL:1	c.1397C>G	p.Thr466Ser	missense	Exon 8 of 8	ENSP00000278302.5	Q9C030-1
	TRIM6	ENST00000380107.5	TSL:1	c.1319C>G	p.Thr440Ser	missense	Exon 9 of 9	ENSP00000369450.1	E9PFM0

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	10
DANN	Benign	0.89
DEOGEN2	Benign	0.0028	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.067	N
LIST_S2	Benign	0.18	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.039	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.24	N
PhyloP100		0.098
PROVEAN	Benign	0.030	N
REVEL	Benign	0.029
Sift	Benign	0.31	T
Sift4G	Benign	0.81	T
Polyphen		0.0050	B
Vest4		0.078
MutPred		0.44		Loss of ubiquitination at K461 (P = 0.1498)
MVP		0.25
MPC		0.027
ClinPred		0.045	T
GERP RS		2.1
Varity_R		0.033
gMVP		0.18
Mutation Taster		=100/0	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: rs145524814; hg19: chr11-5632502;