rs16913748

chr11-6457389-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_033278.4(TRIM3):c.603C>T(p.Ile201=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 1,613,888 control chromosomes in the GnomAD database, including 31,799 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 (3535 hom., cov: 33)
  • Exomes 𝑓: 0.19 (28264 hom.)
• Consequence: TRIM3 NM_033278.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.62

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP7: Synonymous conserved (PhyloP=1.62 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIM3	NM_033278.4	c.603C>T	p.Ile201=	synonymous_variant	5/12	ENST00000345851.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIM3	ENST00000345851.8	c.603C>T	p.Ile201=	synonymous_variant	5/12	1	NM_033278.4	P1

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31434 AN: 152124 Hom.: 3531 Cov.: 33

Gnomad AFR AF: 0.280

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.173

Gnomad ASJ AF: 0.248

Gnomad EAS AF: 0.0158

Gnomad SAS AF: 0.226

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.232

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.204

GnomAD3 exomes AF: 0.179 AC: 45047 AN: 251218 Hom.: 4617 AF XY: 0.183 AC XY: 24869 AN XY: 135810

Gnomad AFR exome AF: 0.279

Gnomad AMR exome AF: 0.137

Gnomad ASJ exome AF: 0.237

Gnomad EAS exome AF: 0.0151

Gnomad SAS exome AF: 0.235

Gnomad FIN exome AF: 0.131

Gnomad NFE exome AF: 0.193

Gnomad OTH exome AF: 0.193

GnomAD4 exome AF: 0.192 AC: 280205 AN: 1461646 Hom.: 28264 Cov.: 34 AF XY: 0.194 AC XY: 140798 AN XY: 727124

Gnomad4 AFR exome AF: 0.280

Gnomad4 AMR exome AF: 0.143

Gnomad4 ASJ exome AF: 0.231

Gnomad4 EAS exome AF: 0.0231

Gnomad4 SAS exome AF: 0.235

Gnomad4 FIN exome AF: 0.135

Gnomad4 NFE exome AF: 0.195

Gnomad4 OTH exome AF: 0.198

GnomAD4 genome AF: 0.207 AC: 31454 AN: 152242 Hom.: 3535 Cov.: 33 AF XY: 0.201 AC XY: 15000 AN XY: 74454

Gnomad4 AFR AF: 0.280

Gnomad4 AMR AF: 0.173

Gnomad4 ASJ AF: 0.248

Gnomad4 EAS AF: 0.0158

Gnomad4 SAS AF: 0.226

Gnomad4 FIN AF: 0.122

Gnomad4 NFE AF: 0.195

Gnomad4 OTH AF: 0.203

Alfa AF: 0.203 Hom.: 4181

Bravo AF: 0.212

Asia WGS AF: 0.122 AC: 425 AN: 3478

EpiCase AF: 0.202

EpiControl AF: 0.210

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
Cadd	Benign	8.6
Dann	Benign	0.83

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: rs16913748; hg19: chr11-6478619; COSMIC: COSV61984837; COSMIC: COSV61984837;