chr11-5597187-T-C

Variant names:

• chr11-5597187-T-C
• rs7927012
• NM_001003818.3:c.17+273T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.551 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM6	NM_001003818.3	MANE Select	c.17+273T>C		intron	N/A	NP_001003818.1
	TRIM6-TRIM34	NM_001003819.4		c.17+273T>C		intron	N/A	NP_001003819.1
	TRIM6	NM_058166.5		c.-68+1006T>C		intron	N/A	NP_477514.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM6	ENST00000380097.8	TSL:1 MANE Select	c.17+273T>C		intron	N/A	ENSP00000369440.3
	TRIM6-TRIM34	ENST00000354852.5	TSL:2	c.17+273T>C		intron	N/A	ENSP00000346916.5
	TRIM6	ENST00000278302.9	TSL:1	c.-68+1006T>C		intron	N/A	ENSP00000278302.5

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

African (AFR) AF: 0.396 AC: 16375 AN: 41368

American (AMR) AF: 0.530 AC: 8072 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.553 AC: 1918 AN: 3468

East Asian (EAS) AF: 0.484 AC: 2482 AN: 5126

South Asian (SAS) AF: 0.404 AC: 1941 AN: 4808

European-Finnish (FIN) AF: 0.541 AC: 5699 AN: 10538

Middle Eastern (MID) AF: 0.712 AC: 208 AN: 292

European-Non Finnish (NFE) AF: 0.556 AC: 37728 AN: 67844

Other (OTH) AF: 0.538 AC: 1132 AN: 2104

Alfa AF: 0.547 Hom.: 28286

Bravo AF: 0.497

Asia WGS AF: 0.428 AC: 1491 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.0
DANN	Benign	0.35
PhyloP100		-0.84
PromoterAI		-0.017	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: rs7927012; hg19: chr11-5618417;