Genetic Variant TRIM21:p.Glu323Asp (chr11-4385744-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003141.4(TRIM21):c.969G>C(p.Glu323Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,106 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

TRIM21
NM_003141.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.457

Publications

0 publications found

Variant links:

Genes affected

TRIM21 (HGNC:11312): (tripartite motif containing 21) This gene encodes a member of the tripartite motif (TRIM) family. 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. The encoded protein is part of the RoSSA ribonucleoprotein, which includes a single polypeptide and one of four small RNA molecules. The RoSSA particle localizes to both the cytoplasm and the nucleus. RoSSA interacts with autoantigens in patients with Sjogren syndrome and systemic lupus erythematosus. Alternatively spliced transcript variants for this gene have been described but the full-length nature of only one has been determined. [provided by RefSeq, Jul 2008]

TRIM21 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14358935).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIM21	NM_003141.4 link	c.969G>C	p.Glu323Asp	missense_variant	Exon 7 of 7	ENST00000254436.8	NP_003132.2	P19474-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIM21	ENST00000254436.8 link	c.969G>C	p.Glu323Asp	missense_variant	Exon 7 of 7	1	NM_003141.4	ENSP00000254436.7		P19474-1
TRIM21	ENST00000533692.1 link	c.141G>C	p.Glu47Asp	missense_variant	Exon 2 of 3	3		ENSP00000434053.1		H0YDP8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461106

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726738

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33474

American (AMR)

AF:

0.00

AC:

AN:

44634

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26120

East Asian (EAS)

AF:

0.00

AC:

AN:

39674

South Asian (SAS)

AF:

0.0000232

AC:

AN:

86024

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53372

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111680

Other (OTH)

AF:

0.0000166

AC:

AN:

60360

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 10, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.969G>C (p.E323D) alteration is located in exon 7 (coding exon 6) of the TRIM21 gene. This alteration results from a G to C substitution at nucleotide position 969, causing the glutamic acid (E) at amino acid position 323 to be replaced by an aspartic acid (D). 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

0.18

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.69

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.19

Eigen

Benign

-0.11

Eigen_PC

Benign

-0.16

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.52

M_CAP

Benign

0.0046

MetaRNN

Benign

0.14

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.3

PhyloP100

0.46

PrimateAI

Benign

0.27

PROVEAN

Benign

-1.9

REVEL

Benign

0.025

Sift

Benign

0.52

Sift4G

Benign

0.15

Polyphen

0.026

Vest4

0.045

MutPred

0.31

Gain of catalytic residue at D326 (P = 0.1877);

MVP

0.46

MPC

0.043

ClinPred

0.079

GERP RS

1.3

PromoterAI

0.0012

Neutral

(source)

Varity_R

0.075

gMVP

0.16

Mutation Taster

=93/7

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over