rs4144331

chr11-4385249-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003141.4(TRIM21):c.*36C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 1,566,640 control chromosomes in the GnomAD database, including 9,348 homozygotes. 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: 𝑓 0.12 (1270 hom., cov: 32)
  • Exomes 𝑓: 0.10 (8078 hom.)
• Consequence: TRIM21 NM_003141.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.192 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIM21	NM_003141.4	c.*36C>A		3_prime_UTR_variant	7/7	ENST00000254436.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIM21	ENST00000254436.8	c.*36C>A		3_prime_UTR_variant	7/7	1	NM_003141.4	P1
TRIM21	ENST00000533692.1	c.*83C>A		3_prime_UTR_variant	3/3	3

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18572 AN: 151976 Hom.: 1264 Cov.: 32

Gnomad AFR AF: 0.178

Gnomad AMI AF: 0.0724

Gnomad AMR AF: 0.0854

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.202

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.0734

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0965

Gnomad OTH AF: 0.109

GnomAD3 exomes AF: 0.114 AC: 24560 AN: 215920 Hom.: 1618 AF XY: 0.115 AC XY: 13391 AN XY: 116046

Gnomad AFR exome AF: 0.182

Gnomad AMR exome AF: 0.0707

Gnomad ASJ exome AF: 0.125

Gnomad EAS exome AF: 0.209

Gnomad SAS exome AF: 0.157

Gnomad FIN exome AF: 0.0739

Gnomad NFE exome AF: 0.0975

Gnomad OTH exome AF: 0.108

GnomAD4 exome AF: 0.103 AC: 145007 AN: 1414546 Hom.: 8078 Cov.: 28 AF XY: 0.104 AC XY: 72703 AN XY: 700268

Gnomad4 AFR exome AF: 0.186

Gnomad4 AMR exome AF: 0.0692

Gnomad4 ASJ exome AF: 0.126

Gnomad4 EAS exome AF: 0.164

Gnomad4 SAS exome AF: 0.153

Gnomad4 FIN exome AF: 0.0768

Gnomad4 NFE exome AF: 0.0952

Gnomad4 OTH exome AF: 0.118

GnomAD4 genome AF: 0.122 AC: 18591 AN: 152094 Hom.: 1270 Cov.: 32 AF XY: 0.120 AC XY: 8946 AN XY: 74350

Gnomad4 AFR AF: 0.178

Gnomad4 AMR AF: 0.0853

Gnomad4 ASJ AF: 0.124

Gnomad4 EAS AF: 0.202

Gnomad4 SAS AF: 0.163

Gnomad4 FIN AF: 0.0734

Gnomad4 NFE AF: 0.0965

Gnomad4 OTH AF: 0.107

Alfa AF: 0.0981 Hom.: 805

Bravo AF: 0.124

Asia WGS AF: 0.168 AC: 585 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.39
Dann	Benign	0.49
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Other links and lift over

dbSNP: rs4144331; hg19: chr11-4406479; COSMIC: COSV54342940;