11-5597187-T-C

Position:

• chr11-5597187-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001003818.3(TRIM6):​c.17+273T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.501 in 151,692 control chromosomes in the GnomAD database, including 19,480 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.50 (19480 hom., cov: 31)
• Consequence: TRIM6 NM_001003818.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.845

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.551 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM6	NM_001003818.3	c.17+273T>C		intron_variant		ENST00000380097.8	NP_001003818.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM6	ENST00000380097.8	c.17+273T>C		intron_variant		1	NM_001003818.3	ENSP00000369440.3
TRIM6-TRIM34	ENST00000354852.5	c.17+273T>C		intron_variant		2		ENSP00000346916.5
ENSG00000239920	ENST00000380259.7	n.*422-1837A>G		intron_variant		5		ENSP00000369609.3

Frequencies

GnomAD3 genomes AF: 0.502 AC: 76020 AN: 151572 Hom.: 19467 Cov.: 31

Gnomad AFR AF: 0.396

Gnomad AMI AF: 0.569

Gnomad AMR AF: 0.530

Gnomad ASJ AF: 0.553

Gnomad EAS AF: 0.484

Gnomad SAS AF: 0.403

Gnomad FIN AF: 0.541

Gnomad MID AF: 0.708

Gnomad NFE AF: 0.556

Gnomad OTH AF: 0.537

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

GnomAD4 genome AF: 0.501 AC: 76072 AN: 151692 Hom.: 19480 Cov.: 31 AF XY: 0.499 AC XY: 36968 AN XY: 74104

Gnomad4 AFR AF: 0.396

Gnomad4 AMR AF: 0.530

Gnomad4 ASJ AF: 0.553

Gnomad4 EAS AF: 0.484

Gnomad4 SAS AF: 0.404

Gnomad4 FIN AF: 0.541

Gnomad4 NFE AF: 0.556

Gnomad4 OTH AF: 0.538

Alfa AF: 0.554 Hom.: 21974

Bravo AF: 0.497

Asia WGS AF: 0.428 AC: 1491 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.0
DANN	Benign	0.35

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

LitVar

Other links and lift over

dbSNP: rs7927012; hg19: chr11-5618417;