11-5611116-C-T

Variant names:

• chr11-5611116-C-T
• NM_001003818.3:c.1325C>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001003818.3(TRIM6):​c.1325C>T​(p.Ala442Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TRIM6 NM_001003818.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.85

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIM6	NM_001003818.3	c.1325C>T	p.Ala442Val	missense_variant	Exon 8 of 8	ENST00000380097.8	NP_001003818.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIM6	ENST00000380097.8	c.1325C>T	p.Ala442Val	missense_variant	Exon 8 of 8	1	NM_001003818.3	ENSP00000369440.3
TRIM6-TRIM34	ENST00000354852.5	c.985+555C>T		intron_variant	Intron 7 of 13	2		ENSP00000346916.5
ENSG00000239920	ENST00000380259.7	n.*421+15485G>A		intron_variant	Intron 3 of 7	5		ENSP00000369609.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 19, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1325C>T (p.A442V) alteration is located in exon 8 (coding exon 8) of the TRIM6 gene. This alteration results from a C to T substitution at nucleotide position 1325, causing the alanine (A) at amino acid position 442 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Uncertain	0.068	T
BayesDel_noAF	Benign	-0.14
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.087	T;.;.;.;.;.;.;.
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.82	T;.;.;T;.;.;T;T
M_CAP	Uncertain	0.097	D
MetaRNN	Uncertain	0.44	T;T;T;T;T;T;T;T
MetaSVM	Uncertain	-0.25	T
MutationAssessor	Benign	1.8	L;.;.;.;.;.;.;.
PROVEAN	Benign	-2.2	N;N;N;N;N;N;N;.
REVEL	Uncertain	0.53
Sift	Benign	0.20	T;T;T;T;T;T;T;.
Sift4G	Benign	0.20	T;T;T;T;T;T;T;T
Polyphen		0.99	D;.;D;D;.;.;.;D
Vest4		0.32
MutPred		0.71		Gain of sheet (P = 0.0827);.;.;.;.;.;.;.;
MVP		0.78
MPC		0.14
ClinPred		0.92	D
GERP RS		4.1
Varity_R		0.091
gMVP		0.39

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-5632346;