rs11605141

chr11-6457154-C-T

Variant summary

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

The NM_033278.4(TRIM3):c.697-125G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 1,511,962 control chromosomes in the GnomAD database, including 30,025 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 0.21 (3578 hom., cov: 33)
  • Exomes 𝑓: 0.19 (26447 hom.)
• Consequence: TRIM3 NM_033278.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.397

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.279 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIM3	NM_033278.4	c.697-125G>A		intron_variant		ENST00000345851.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIM3	ENST00000345851.8	c.697-125G>A		intron_variant		1	NM_033278.4	P1

Frequencies

GnomAD3 genomes AF: 0.208 AC: 31580 AN: 152002 Hom.: 3575 Cov.: 33

Gnomad AFR AF: 0.283

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.243

Gnomad EAS AF: 0.0160

Gnomad SAS AF: 0.227

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.205

GnomAD4 exome AF: 0.192 AC: 261093 AN: 1359842 Hom.: 26447 Cov.: 26 AF XY: 0.194 AC XY: 129876 AN XY: 669710

Gnomad4 AFR exome AF: 0.282

Gnomad4 AMR exome AF: 0.142

Gnomad4 ASJ exome AF: 0.227

Gnomad4 EAS exome AF: 0.0232

Gnomad4 SAS exome AF: 0.236

Gnomad4 FIN exome AF: 0.136

Gnomad4 NFE exome AF: 0.195

Gnomad4 OTH exome AF: 0.199

GnomAD4 genome AF: 0.208 AC: 31598 AN: 152120 Hom.: 3578 Cov.: 33 AF XY: 0.203 AC XY: 15087 AN XY: 74382

Gnomad4 AFR AF: 0.283

Gnomad4 AMR AF: 0.174

Gnomad4 ASJ AF: 0.243

Gnomad4 EAS AF: 0.0160

Gnomad4 SAS AF: 0.227

Gnomad4 FIN AF: 0.123

Gnomad4 NFE AF: 0.195

Gnomad4 OTH AF: 0.204

Alfa AF: 0.204 Hom.: 425

Bravo AF: 0.213

Asia WGS AF: 0.121 AC: 424 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	6.5
Dann	Benign	0.61

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs11605141; hg19: chr11-6478384;