11-5604373-A-G

Variant names:

• chr11-5604373-A-G
• rs7108470
• NM_001003818.3:c.508-161A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001003818.3(TRIM6):​c.508-161A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.446 in 151,942 control chromosomes in the GnomAD database, including 15,643 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 0.45 (15643 hom., cov: 31)
• Consequence: TRIM6 NM_001003818.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.23
• Publications: 9 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.661 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIM6	NM_001003818.3	c.508-161A>G		intron_variant	Intron 2 of 7	ENST00000380097.8	NP_001003818.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIM6	ENST00000380097.8	c.508-161A>G		intron_variant	Intron 2 of 7	1	NM_001003818.3	ENSP00000369440.3
TRIM6-TRIM34	ENST00000354852.5	c.508-161A>G		intron_variant	Intron 2 of 13	2		ENSP00000346916.5
ENSG00000239920	ENST00000380259.7	n.*422-9023T>C		intron_variant	Intron 3 of 7	5		ENSP00000369609.3

Frequencies

GnomAD3 genomes AF: 0.446 AC: 67691 AN: 151822 Hom.: 15603 Cov.: 31

Gnomad AFR AF: 0.502

Gnomad AMI AF: 0.447

Gnomad AMR AF: 0.524

Gnomad ASJ AF: 0.499

Gnomad EAS AF: 0.680

Gnomad SAS AF: 0.542

Gnomad FIN AF: 0.321

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.384

Gnomad OTH AF: 0.491

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

GnomAD4 genome AF: 0.446 AC: 67792 AN: 151942 Hom.: 15643 Cov.: 31 AF XY: 0.447 AC XY: 33232 AN XY: 74272

African (AFR) AF: 0.503 AC: 20817 AN: 41418

American (AMR) AF: 0.525 AC: 8008 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.499 AC: 1732 AN: 3470

East Asian (EAS) AF: 0.680 AC: 3505 AN: 5158

South Asian (SAS) AF: 0.543 AC: 2611 AN: 4812

European-Finnish (FIN) AF: 0.321 AC: 3395 AN: 10564

Middle Eastern (MID) AF: 0.571 AC: 168 AN: 294

European-Non Finnish (NFE) AF: 0.384 AC: 26102 AN: 67948

Other (OTH) AF: 0.497 AC: 1048 AN: 2110

Alfa AF: 0.421 Hom.: 28778

Bravo AF: 0.466

Asia WGS AF: 0.611 AC: 2123 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.99
DANN	Benign	0.42
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

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: rs7108470; hg19: chr11-5625603;