Variant 11-4385418-G-A 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.1295C>T(p.Ser432Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,530 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 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: 6.8e-7 ( 0 hom. )

Consequence

TRIM21
NM_003141.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.98

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 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.1295C>T	p.Ser432Phe	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.1295C>T	p.Ser432Phe	missense_variant	7/7	1	NM_003141.4	P1	P19474-1
TRIM21	ENST00000533692.1 linkuse as main transcript	c.209-24C>T		intron_variant		3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461530

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727018

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:

8.99e-7

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 19, 2024

The c.1295C>T (p.S432F) alteration is located in exon 7 (coding exon 6) of the TRIM21 gene. This alteration results from a C to T substitution at nucleotide position 1295, causing the serine (S) at amino acid position 432 to be replaced by a phenylalanine (F). 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

Uncertain

0.41

BayesDel_addAF

Benign

-0.061

BayesDel_noAF

Benign

-0.33

Cadd

Benign

Dann

Uncertain

1.0

DEOGEN2

Uncertain

0.65

Eigen

Benign

-0.15

Eigen_PC

Benign

-0.088

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.30

M_CAP

Benign

0.081

MetaRNN

Uncertain

0.52

MetaSVM

Benign

-0.42

MutationAssessor

Benign

1.8

MutationTaster

Benign

0.61

N;N

PrimateAI

Benign

0.34

PROVEAN

Uncertain

-2.6

REVEL

Benign

0.20

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0030

Polyphen

0.033

Vest4

0.18

MutPred

0.74

Gain of sheet (P = 0.1451);

MVP

0.76

MPC

0.19

ClinPred

0.98

GERP RS

3.4

Varity_R

0.25

gMVP

0.36

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over