rs11605881

Positions:

• chr11-6474370-A-G

Variant summary

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

The NM_001248006.2(TRIM3):​c.-306T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 152,156 control chromosomes in the GnomAD database, including 2,886 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 0.19 (2884 hom., cov: 32)
  • Exomes 𝑓: 0.29 (2 hom.)
• Consequence: TRIM3 NM_001248006.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.18

Genes affected

TRIM3 (HGNC:10064): (tripartite motif containing 3) The protein encoded by this gene is a member of the tripartite motif (TRIM) family, also called the 'RING-B-box-coiled-coil' (RBCC) subgroup of RING finger proteins. 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 protein localizes to cytoplasmic filaments. It is similar to a rat protein which is a specific partner for the tail domain of myosin V, a class of myosins which are involved in the targeted transport of organelles. The rat protein can also interact with alpha-actinin-4. Thus it is suggested that this human protein may play a role in myosin V-mediated cargo transport. Alternatively spliced transcript variants encoding the same isoform have been identified. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.249 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM3	NM_001248006.2	c.-306T>C		5_prime_UTR_variant	1/12		NP_001234935.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM3	ENST00000525074.5	c.-306T>C		5_prime_UTR_variant	1/12	2		ENSP00000433102.1
TRIM3	ENST00000529529.1	c.-471T>C		5_prime_UTR_variant	1/4	4		ENSP00000437283.1

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28438 AN: 152004 Hom.: 2880 Cov.: 32

Gnomad AFR AF: 0.253

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.162

Gnomad ASJ AF: 0.245

Gnomad EAS AF: 0.0257

Gnomad SAS AF: 0.212

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.174

Gnomad OTH AF: 0.187

GnomAD4 exome AF: 0.294 AC: 10 AN: 34 Hom.: 2 Cov.: 0 AF XY: 0.375 AC XY: 9 AN XY: 24

Gnomad4 NFE exome AF: 0.294

GnomAD4 genome AF: 0.187 AC: 28456 AN: 152122 Hom.: 2884 Cov.: 32 AF XY: 0.184 AC XY: 13649 AN XY: 74378

Gnomad4 AFR AF: 0.253

Gnomad4 AMR AF: 0.161

Gnomad4 ASJ AF: 0.245

Gnomad4 EAS AF: 0.0258

Gnomad4 SAS AF: 0.212

Gnomad4 FIN AF: 0.103

Gnomad4 NFE AF: 0.174

Gnomad4 OTH AF: 0.185

Alfa AF: 0.181 Hom.: 3249

Bravo AF: 0.193

Asia WGS AF: 0.119 AC: 415 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	13
DANN	Benign	0.44

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: rs11605881; hg19: chr11-6495600;