Genetic Variant TRIM3:p.Ile201Ile (chr11-6457389-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.62

Publications

16 publications found

Variant links:

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]

TRIM3 links:

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ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIM3	NM_033278.4 link	c.603C>T	p.Ile201Ile	synonymous_variant	Exon 5 of 12	ENST00000345851.8	NP_150594.2	O75382-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIM3	ENST00000345851.8 link	c.603C>T	p.Ile201Ile	synonymous_variant	Exon 5 of 12	1	NM_033278.4	ENSP00000340797.3		O75382-1

Frequencies

GnomAD3 genomes

AF:

0.207

AC:

31434

AN:

152124

Hom.:

3531

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.194

AC XY:

140798

AN XY:

727124

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

14123

28246

42370

56493

70616

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7572

15144

22716

30288

37860

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.207

AC:

31454

AN:

152242

Hom.:

3535

Cov.:

AF XY:

0.201

AC XY:

15000

AN XY:

74454

show subpopulations

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:

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:

AN:

292

European-Non Finnish (NFE)

AF:

0.195

AC:

13263

AN:

68008

Other (OTH)

AF:

0.203

AC:

429

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1278

2557

3835

5114

6392

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

328

656

984

1312

1640

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

8.6

(source)

DANN

Benign

0.83

PhyloP100

1.6

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over