Variant 11-6456956-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_033278.4(TRIM3):c.770A>G(p.Gln257Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000412 in 1,457,034 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

TRIM3
NM_033278.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.57

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:

TRIM3 (HGNC:):

TRIM3 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.33644468).

BS2

High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM3	NM_033278.4 linkuse as main transcript	c.770A>G	p.Gln257Arg	missense_variant	6/12	ENST00000345851.8	NP_150594.2	O75382-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM3	ENST00000345851.8 linkuse as main transcript	c.770A>G	p.Gln257Arg	missense_variant	6/12	1	NM_033278.4	ENSP00000340797.3		O75382-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000404

AC:

AN:

247820

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134372

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000881

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000412

AC:

AN:

1457034

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

724918

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000540

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 03, 2024

The c.770A>G (p.Q257R) alteration is located in exon 7 (coding exon 5) of the TRIM3 gene. This alteration results from a A to G substitution at nucleotide position 770, causing the glutamine (Q) at amino acid position 257 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

-0.080

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.28

T;T;.;T;.;T

Eigen

Benign

0.18

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.89

.;.;D;D;D;D

M_CAP

Uncertain

0.090

MetaRNN

Benign

0.34

T;T;T;T;T;T

MetaSVM

Uncertain

-0.15

MutationAssessor

Benign

1.9

L;L;.;L;.;.

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-2.2

N;N;N;N;.;N

REVEL

Benign

0.22

Sift

Uncertain

0.0050

D;D;D;D;.;D

Sift4G

Uncertain

0.0060

D;D;D;D;.;.

Polyphen

0.28

B;B;.;B;.;.

Vest4

0.41

MutPred

0.33

Gain of helix (P = 0.0325);Gain of helix (P = 0.0325);.;Gain of helix (P = 0.0325);.;Gain of helix (P = 0.0325);

MVP

0.72

MPC

1.3

ClinPred

0.76

GERP RS

5.3

Varity_R

0.26

gMVP

0.40

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over