rs955022236

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_033278.4(TRIM3):c.712C>A(p.Leu238Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000315 in 1,589,712 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

TRIM3
NM_033278.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.99

Publications

0 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.27670974).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TRIM3	NM_033278.4	MANE Select	c.712C>A	p.Leu238Met	missense	Exon 6 of 12	NP_150594.2
TRIM3	NM_001248006.2		c.712C>A	p.Leu238Met	missense	Exon 6 of 12	NP_001234935.1	O75382-1
TRIM3	NM_006458.4		c.712C>A	p.Leu238Met	missense	Exon 7 of 13	NP_006449.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TRIM3	ENST00000345851.8	TSL:1 MANE Select	c.712C>A	p.Leu238Met	missense	Exon 6 of 12	ENSP00000340797.3	O75382-1
TRIM3	ENST00000359518.7	TSL:5	c.712C>A	p.Leu238Met	missense	Exon 7 of 13	ENSP00000352508.3	O75382-1
TRIM3	ENST00000525074.5	TSL:2	c.712C>A	p.Leu238Met	missense	Exon 6 of 12	ENSP00000433102.1	O75382-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152272

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000124

AC:

AN:

242010

AF XY:

0.0000152

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000268

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000278

AC:

AN:

1437440

Hom.:

Cov.:

AF XY:

0.00000281

AC XY:

AN XY:

711754

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33186

American (AMR)

AF:

0.00

AC:

AN:

44404

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25882

East Asian (EAS)

AF:

0.00

AC:

AN:

39232

South Asian (SAS)

AF:

0.00

AC:

AN:

85760

European-Finnish (FIN)

AF:

0.00

AC:

AN:

44546

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5686

European-Non Finnish (NFE)

AF:

0.00000364

AC:

AN:

1099234

Other (OTH)

AF:

0.00

AC:

AN:

59510

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.538

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.00000657

AC:

AN:

152272

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74396

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41474

American (AMR)

AF:

0.00

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5200

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10632

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68048

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Uncertain

0.049

BayesDel_noAF

Benign

-0.17

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.14

Eigen

Benign

0.0057

Eigen_PC

Benign

-0.070

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.92

M_CAP

Benign

0.045

MetaRNN

Benign

0.28

MetaSVM

Uncertain

-0.018

MutationAssessor

Uncertain

2.1

PhyloP100

2.0

PrimateAI

Uncertain

0.79

PROVEAN

Benign

0.17

REVEL

Uncertain

0.29

Sift

Benign

0.095

Sift4G

Benign

0.10

Polyphen

0.97

Vest4

0.52

MutPred

0.34

Loss of helix (P = 0.0376)

MVP

0.39

MPC

2.2

ClinPred

0.27

GERP RS

-0.12

Varity_R

0.13

gMVP

0.25

Mutation Taster

=53/47

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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