Variant 11-4385614-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_003141.4(TRIM21):c.1099G>A(p.Gly367Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,528 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

TRIM21
NM_003141.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.92

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIM21	NM_003141.4 linkuse as main transcript	c.1099G>A	p.Gly367Arg	missense_variant	7/7	ENST00000254436.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIM21	ENST00000254436.8 linkuse as main transcript	c.1099G>A	p.Gly367Arg	missense_variant	7/7	1	NM_003141.4	P1	P19474-1
TRIM21	ENST00000533692.1 linkuse as main transcript	c.208+64G>A		intron_variant		3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000406

AC:

AN:

246296

Hom.:

AF XY:

0.00000749

AC XY:

AN XY:

133506

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000562

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460528

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726380

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 23, 2024

The c.1099G>A (p.G367R) alteration is located in exon 7 (coding exon 6) of the TRIM21 gene. This alteration results from a G to A substitution at nucleotide position 1099, causing the glycine (G) at amino acid position 367 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

Pathogenic

0.76

BayesDel_addAF

Benign

-0.095

BayesDel_noAF

Benign

-0.20

Cadd

Benign

Dann

Uncertain

1.0

DEOGEN2

Benign

0.38

Eigen

Uncertain

0.42

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.74

M_CAP

Benign

0.050

MetaRNN

Uncertain

0.56

MetaSVM

Uncertain

-0.28

MutationAssessor

Uncertain

2.7

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-2.2

REVEL

Uncertain

0.43

Sift

Benign

0.099

Sift4G

Benign

0.45

Polyphen

1.0

Vest4

0.37

MutPred

0.62

Gain of MoRF binding (P = 0.0269);

MVP

0.89

MPC

0.33

ClinPred

0.76

GERP RS

4.0

Varity_R

0.14

gMVP

0.46

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