11-5611218-A-C

Position:

• chr11-5611218-A-C

Variant summary

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

The NM_001003818.3(TRIM6):​c.1427A>C​(p.Asn476Thr) variant causes a missense change. 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: 4.80

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:):

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/exons	MANE	Protein	UniProt
TRIM6	NM_001003818.3	c.1427A>C	p.Asn476Thr	missense_variant	8/8	ENST00000380097.8	NP_001003818.1
TRIM6-TRIM34	NM_001003819.4	c.985+657A>C		intron_variant			NP_001003819.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM6	ENST00000380097.8	c.1427A>C	p.Asn476Thr	missense_variant	8/8	1	NM_001003818.3	ENSP00000369440

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 04, 2022

The c.1427A>C (p.N476T) alteration is located in exon 8 (coding exon 8) of the TRIM6 gene. This alteration results from a A to C substitution at nucleotide position 1427, causing the asparagine (N) at amino acid position 476 to be replaced by a threonine (T). 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	Pathogenic	0.73
BayesDel_addAF	Uncertain	0.093	D
BayesDel_noAF	Benign	-0.10
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T;.;.;.;.;.;.;.
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.92	D;.;.;D;.;.;D;D
M_CAP	Uncertain	0.21	D
MetaRNN	Uncertain	0.70	D;D;D;D;D;D;D;D
MetaSVM	Uncertain	0.063	D
MutationAssessor	Pathogenic	4.1	H;.;.;.;.;.;.;.
MutationTaster	Benign	1.0	D;D;N;N;N;N;N;N;N;D
PROVEAN	Pathogenic	-5.0	D;D;D;D;D;D;D;.
REVEL	Uncertain	0.41
Sift	Uncertain	0.0010	D;D;D;D;D;D;D;.
Sift4G	Uncertain	0.0020	D;D;D;D;D;D;D;D
Polyphen		0.75	P;.;D;P;.;.;.;D
Vest4		0.32
MutPred		0.82		Loss of sheet (P = 0.1158);.;.;.;.;.;.;.;
MVP		0.81
MPC		0.22
ClinPred		0.99	D
GERP RS		3.0
Varity_R		0.40
gMVP		0.38

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: chr11-5632448;