11-4386167-C-A

Position:

• chr11-4386167-C-A

Variant summary

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

The NM_003141.4(TRIM21):​c.849G>T​(p.Arg283Ser) 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 (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TRIM21 NM_003141.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.827

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]

ACMG classification

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	c.849G>T	p.Arg283Ser	missense_variant	6/7	ENST00000254436.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIM21	ENST00000254436.8	c.849G>T	p.Arg283Ser	missense_variant	6/7	1	NM_003141.4	P1
TRIM21	ENST00000533692.1	c.24G>T	p.Arg8Ser	missense_variant	1/3	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 14, 2023

The c.849G>T (p.R283S) alteration is located in exon 6 (coding exon 5) of the TRIM21 gene. This alteration results from a G to T substitution at nucleotide position 849, causing the arginine (R) at amino acid position 283 to be replaced by a serine (S). 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	0.50
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.46	T
Eigen	Benign	-0.056
Eigen_PC	Benign	-0.12
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.73	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L
MutationTaster	Benign	0.56	N;N
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-4.0	D
REVEL	Benign	0.11
Sift	Uncertain	0.015	D
Sift4G	Uncertain	0.0040	D
Polyphen		0.88	P
Vest4		0.63
MutPred		0.55		Gain of ubiquitination at K280 (P = 0.072);
MVP		0.59
MPC		0.25
ClinPred		0.81	D
GERP RS		2.8
Varity_R		0.33
gMVP		0.30

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-4407397;