Genetic Variant NM_001248006.2:c.-306T>C (chr11-6474370-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.18

Publications

6 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 -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 rank	MANE	Protein	UniProt
TRIM3	NM_001248006.2 link	c.-306T>C		5_prime_UTR_variant	Exon 1 of 12		NP_001234935.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIM3	ENST00000525074.5 link	c.-306T>C		5_prime_UTR_variant	Exon 1 of 12	2		ENSP00000433102.1
TRIM3	ENST00000529529.1 link	c.-471T>C		5_prime_UTR_variant	Exon 1 of 4	4		ENSP00000437283.1

Frequencies

GnomAD3 genomes

AF:

0.187

AC:

28438

AN:

152004

Hom.:

2880

Cov.:

show subpopulations

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:

AN:

Hom.:

Cov.:

AF XY:

0.375

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.294

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.187

AC:

28456

AN:

152122

Hom.:

2884

Cov.:

AF XY:

0.184

AC XY:

13649

AN XY:

74378

show subpopulations

African (AFR)

AF:

0.253

AC:

10493

AN:

41486

American (AMR)

AF:

0.161

AC:

2470

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.245

AC:

848

AN:

3466

East Asian (EAS)

AF:

0.0258

AC:

133

AN:

5164

South Asian (SAS)

AF:

0.212

AC:

1022

AN:

4820

European-Finnish (FIN)

AF:

0.103

AC:

1089

AN:

10598

Middle Eastern (MID)

AF:

0.221

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.174

AC:

11852

AN:

67970

Other (OTH)

AF:

0.185

AC:

392

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1179

2358

3537

4716

5895

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

304

608

912

1216

1520

<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:

0.185

Hom.:

6230

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

(source)

DANN

Benign

0.44

PhyloP100

2.2

PromoterAI

0.037

Neutral

(source)

Mutation Taster

=284/16

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over