Genetic Variant TRIM3:p.Arg356Leu (chr11-6456659-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_033278.4(TRIM3):c.1067G>T(p.Arg356Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TRIM3
NM_033278.4 missense

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 1.01

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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.1067G>T	p.Arg356Leu	missense	Exon 6 of 12	NP_150594.2
TRIM3	NM_001248006.2		c.1067G>T	p.Arg356Leu	missense	Exon 6 of 12	NP_001234935.1	O75382-1
TRIM3	NM_006458.4		c.1067G>T	p.Arg356Leu	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.1067G>T	p.Arg356Leu	missense	Exon 6 of 12	ENSP00000340797.3	O75382-1
TRIM3	ENST00000359518.7	TSL:5	c.1067G>T	p.Arg356Leu	missense	Exon 7 of 13	ENSP00000352508.3	O75382-1
TRIM3	ENST00000525074.5	TSL:2	c.1067G>T	p.Arg356Leu	missense	Exon 6 of 12	ENSP00000433102.1	O75382-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1455462

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

723256

African (AFR)

AF:

0.00

AC:

AN:

33388

American (AMR)

AF:

0.00

AC:

AN:

44614

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26056

East Asian (EAS)

AF:

0.00

AC:

AN:

39556

South Asian (SAS)

AF:

0.00

AC:

AN:

86116

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51196

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1108654

Other (OTH)

AF:

0.00

AC:

AN:

60126

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

Autism (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.36

BayesDel_addAF

Uncertain

0.065

BayesDel_noAF

Benign

-0.14

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.62

Eigen

Uncertain

0.22

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.93

M_CAP

Uncertain

0.14

MetaRNN

Uncertain

0.70

MetaSVM

Uncertain

-0.12

MutationAssessor

Benign

1.7

PhyloP100

1.0

PrimateAI

Uncertain

0.70

PROVEAN

Uncertain

-2.9

REVEL

Uncertain

0.49

Sift

Uncertain

0.0060

Sift4G

Uncertain

0.0050

Polyphen

0.80

Vest4

0.59

MutPred

0.73

Loss of MoRF binding (P = 0.0075)

MVP

0.47

MPC

2.0

ClinPred

0.97

GERP RS

5.3

Varity_R

0.33

gMVP

0.94

Mutation Taster

=50/50

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over