11-5620771-T-C

Position:

• chr11-5620771-T-C

Variant summary

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

The NM_001003819.4(TRIM6-TRIM34):​c.985+10210T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 152,020 control chromosomes in the GnomAD database, including 6,352 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 0.29 (6352 hom., cov: 31)
• Consequence: TRIM6-TRIM34 NM_001003819.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.50

Genes affected

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]

TRIM34 (HGNC:10063): (tripartite motif containing 34) 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. Expression of this gene is up-regulated by interferon. 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 the upstream TRIM6 gene has also been observed, which results in a fusion product from these neighboring family members. [provided by RefSeq, Oct 2010]

ENSG00000239920 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM6-TRIM34	NM_001003819.4	c.985+10210T>C		intron_variant			NP_001003819.1
TRIM34	NM_001003827.1	c.-78+748T>C		intron_variant			NP_001003827.1
TRIM5	XR_001748014.3	n.1342+24914A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM6-TRIM34	ENST00000354852.5	c.985+10210T>C		intron_variant		2		ENSP00000346916.5
ENSG00000239920	ENST00000380259.7	n.*421+5830A>G		intron_variant		5		ENSP00000369609.3

Frequencies

GnomAD3 genomes AF: 0.288 AC: 43694 AN: 151900 Hom.: 6346 Cov.: 31

Gnomad AFR AF: 0.283

Gnomad AMI AF: 0.466

Gnomad AMR AF: 0.256

Gnomad ASJ AF: 0.268

Gnomad EAS AF: 0.299

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.327

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.296

Gnomad OTH AF: 0.288

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

GnomAD4 genome AF: 0.288 AC: 43735 AN: 152020 Hom.: 6352 Cov.: 31 AF XY: 0.286 AC XY: 21281 AN XY: 74300

Gnomad4 AFR AF: 0.283

Gnomad4 AMR AF: 0.256

Gnomad4 ASJ AF: 0.268

Gnomad4 EAS AF: 0.300

Gnomad4 SAS AF: 0.199

Gnomad4 FIN AF: 0.327

Gnomad4 NFE AF: 0.296

Gnomad4 OTH AF: 0.290

Alfa AF: 0.288 Hom.: 13096

Bravo AF: 0.285

Asia WGS AF: 0.261 AC: 907 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.7
DANN	Benign	0.77

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: rs7939159; hg19: chr11-5642001;