rs16913748

Variant names:

• chr11-6457389-G-A
• rs16913748
• NM_033278.4:c.603C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_033278.4(TRIM3):​c.603C>T​(p.Ile201Ile) 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
• Publications: 16 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033278.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM3	NM_033278.4	MANE Select	c.603C>T	p.Ile201Ile	synonymous	Exon 5 of 12	NP_150594.2
	TRIM3	NM_001248006.2		c.603C>T	p.Ile201Ile	synonymous	Exon 5 of 12	NP_001234935.1
	TRIM3	NM_006458.4		c.603C>T	p.Ile201Ile	synonymous	Exon 6 of 13	NP_006449.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM3	ENST00000345851.8	TSL:1 MANE Select	c.603C>T	p.Ile201Ile	synonymous	Exon 5 of 12	ENSP00000340797.3
	TRIM3	ENST00000359518.7	TSL:5	c.603C>T	p.Ile201Ile	synonymous	Exon 6 of 13	ENSP00000352508.3
	TRIM3	ENST00000525074.5	TSL:2	c.603C>T	p.Ile201Ile	synonymous	Exon 5 of 12	ENSP00000433102.1

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

GnomAD2 exomes AF: 0.179 AC: 45047 AN: 251218 AF XY: 0.183

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 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

African (AFR) AF: 0.280 AC: 9388 AN: 33478

American (AMR) AF: 0.143 AC: 6401 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.231 AC: 6033 AN: 26136

East Asian (EAS) AF: 0.0231 AC: 919 AN: 39700

South Asian (SAS) AF: 0.235 AC: 20253 AN: 86248

European-Finnish (FIN) AF: 0.135 AC: 7180 AN: 53358

Middle Eastern (MID) AF: 0.212 AC: 1193 AN: 5626

European-Non Finnish (NFE) AF: 0.195 AC: 216879 AN: 1111998

Other (OTH) AF: 0.198 AC: 11959 AN: 60380

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

African (AFR) AF: 0.280 AC: 11629 AN: 41516

American (AMR) AF: 0.173 AC: 2643 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.248 AC: 860 AN: 3472

East Asian (EAS) AF: 0.0158 AC: 82 AN: 5182

South Asian (SAS) AF: 0.226 AC: 1092 AN: 4824

European-Finnish (FIN) AF: 0.122 AC: 1298 AN: 10618

Middle Eastern (MID) AF: 0.226 AC: 66 AN: 292

European-Non Finnish (NFE) AF: 0.195 AC: 13263 AN: 68008

Other (OTH) AF: 0.203 AC: 429 AN: 2116

Alfa AF: 0.199 Hom.: 8349

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	8.6
DANN	Benign	0.83
PhyloP100		1.6
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: rs16913748; hg19: chr11-6478619; COSMIC: COSV61984837; COSMIC: COSV61984837;