chr11-5596757-G-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001003818.3(TRIM6):​c.-141G>T 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 0.00000618 in 1,294,402 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000026 (0 hom., cov: 27)
  • Exomes 𝑓: 0.0000035 (0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001003818.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM6	NM_001003818.3	MANE Select	c.-141G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 8	NP_001003818.1	Q9C030-2
	TRIM6	NM_001003818.3	MANE Select	c.-141G>T		5_prime_UTR	Exon 1 of 8	NP_001003818.1	Q9C030-2
	TRIM6-TRIM34	NM_001003819.4		c.-141G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 14	NP_001003819.1	B2RNG4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM6	ENST00000380097.8	TSL:1 MANE Select	c.-141G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 8	ENSP00000369440.3	Q9C030-2
	TRIM6-TRIM34	ENST00000354852.5	TSL:2	c.-141G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 14	ENSP00000346916.5	B2RNG4
	TRIM6	ENST00000445329.5	TSL:1	c.-388G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 8	ENSP00000399215.1	Q9C030-3

Frequencies

GnomAD3 genomes AF: 0.0000265 AC: 4 AN: 151038 Hom.: 0 Cov.: 27

Gnomad AFR AF: 0.0000975

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000350 AC: 4 AN: 1143364 Hom.: 0 Cov.: 15 AF XY: 0.00000171 AC XY: 1 AN XY: 583450

African (AFR) AF: 0.000111 AC: 3 AN: 26992

American (AMR) AF: 0.00 AC: 0 AN: 40946

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23918

East Asian (EAS) AF: 0.00 AC: 0 AN: 37782

South Asian (SAS) AF: 0.00 AC: 0 AN: 78458

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43312

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4590

European-Non Finnish (NFE) AF: 0.00000119 AC: 1 AN: 837726

Other (OTH) AF: 0.00 AC: 0 AN: 49640

GnomAD4 genome AF: 0.0000265 AC: 4 AN: 151038 Hom.: 0 Cov.: 27 AF XY: 0.0000272 AC XY: 2 AN XY: 73662

African (AFR) AF: 0.0000975 AC: 4 AN: 41034

American (AMR) AF: 0.00 AC: 0 AN: 15188

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3456

East Asian (EAS) AF: 0.00 AC: 0 AN: 5128

South Asian (SAS) AF: 0.00 AC: 0 AN: 4770

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67756

Other (OTH) AF: 0.00 AC: 0 AN: 2080

Alfa AF: 0.00 Hom.: 23355

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.088
DANN	Benign	0.60
PhyloP100		-2.0
PromoterAI		-0.061	Neutral

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;