rs12272467

Variant names:

• chr11-5596757-G-A
• rs12272467
• NM_001003818.3:c.-141G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-5596757-G-A
• chr11-5596757-G-T

Variant summary

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

The NM_001003818.3(TRIM6):​c.-141G>A variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.452 in 1,291,750 control chromosomes in the GnomAD database, including 133,765 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 (15580 hom., cov: 27)
  • Exomes 𝑓: 0.45 (118185 hom.)
• Consequence: TRIM6 NM_001003818.3 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.97
• Publications: 13 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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.478 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIM6	NM_001003818.3	c.-141G>A		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 8	ENST00000380097.8	NP_001003818.1
TRIM6	NM_001003818.3	c.-141G>A		5_prime_UTR_variant	Exon 1 of 8	ENST00000380097.8	NP_001003818.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIM6	ENST00000380097.8	c.-141G>A		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 8	1	NM_001003818.3	ENSP00000369440.3
TRIM6-TRIM34	ENST00000354852.5	c.-141G>A		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 14	2		ENSP00000346916.5
TRIM6	ENST00000380097.8	c.-141G>A		5_prime_UTR_variant	Exon 1 of 8	1	NM_001003818.3	ENSP00000369440.3
TRIM6-TRIM34	ENST00000354852.5	c.-141G>A		5_prime_UTR_variant	Exon 1 of 14	2		ENSP00000346916.5
ENSG00000239920	ENST00000380259.7	n.*422-1407C>T		intron_variant	Intron 3 of 7	5		ENSP00000369609.3

Frequencies

GnomAD3 genomes AF: 0.454 AC: 68509 AN: 150874 Hom.: 15562 Cov.: 27

Gnomad AFR AF: 0.433

Gnomad AMI AF: 0.438

Gnomad AMR AF: 0.487

Gnomad ASJ AF: 0.504

Gnomad EAS AF: 0.490

Gnomad SAS AF: 0.370

Gnomad FIN AF: 0.451

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.459

Gnomad OTH AF: 0.486

GnomAD4 exome AF: 0.452 AC: 515430 AN: 1140756 Hom.: 118185 Cov.: 15 AF XY: 0.449 AC XY: 261498 AN XY: 582198

African (AFR) AF: 0.427 AC: 11493 AN: 26916

American (AMR) AF: 0.450 AC: 18372 AN: 40846

Ashkenazi Jewish (ASJ) AF: 0.504 AC: 12047 AN: 23884

East Asian (EAS) AF: 0.465 AC: 17563 AN: 37734

South Asian (SAS) AF: 0.378 AC: 29648 AN: 78378

European-Finnish (FIN) AF: 0.469 AC: 20286 AN: 43250

Middle Eastern (MID) AF: 0.601 AC: 2756 AN: 4586

European-Non Finnish (NFE) AF: 0.455 AC: 379978 AN: 835620

Other (OTH) AF: 0.470 AC: 23287 AN: 49542

GnomAD4 genome AF: 0.454 AC: 68579 AN: 150994 Hom.: 15580 Cov.: 27 AF XY: 0.454 AC XY: 33451 AN XY: 73710

African (AFR) AF: 0.434 AC: 17818 AN: 41090

American (AMR) AF: 0.487 AC: 7398 AN: 15190

Ashkenazi Jewish (ASJ) AF: 0.504 AC: 1742 AN: 3456

East Asian (EAS) AF: 0.490 AC: 2500 AN: 5104

South Asian (SAS) AF: 0.371 AC: 1763 AN: 4758

European-Finnish (FIN) AF: 0.451 AC: 4684 AN: 10386

Middle Eastern (MID) AF: 0.667 AC: 196 AN: 294

European-Non Finnish (NFE) AF: 0.459 AC: 31059 AN: 67714

Other (OTH) AF: 0.488 AC: 1023 AN: 2098

Alfa AF: 0.462 Hom.: 23355

Bravo AF: 0.456

Asia WGS AF: 0.417 AC: 1454 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.12
DANN	Benign	0.86
PhyloP100		-2.0
PromoterAI		0.20	Neutral
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: rs12272467; hg19: chr11-5617987; COSMIC: COSV53475433; COSMIC: COSV53475433;