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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001248006.2. 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_001248006.2		c.-306T>C		5_prime_UTR	Exon 1 of 12	NP_001234935.1	O75382-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM3	ENST00000525074.5	TSL:2	c.-306T>C		5_prime_UTR	Exon 1 of 12	ENSP00000433102.1	O75382-1
	TRIM3	ENST00000529529.1	TSL:4	c.-471T>C		5_prime_UTR	Exon 1 of 4	ENSP00000437283.1	E9PMW5

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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over