11-4385249-G-T

Variant names:

• chr11-4385249-G-T
• rs4144331
• NM_003141.4:c.*36C>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TRIM21	NM_003141.4	c.*36C>A		3_prime_UTR_variant	Exon 7 of 7	ENST00000254436.8	NP_003132.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIM21	ENST00000254436.8	c.*36C>A		3_prime_UTR_variant	Exon 7 of 7	1	NM_003141.4	ENSP00000254436.7
TRIM21	ENST00000533692.1	c.*83C>A		3_prime_UTR_variant	Exon 3 of 3	3		ENSP00000434053.1

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

GnomAD2 exomes AF: 0.114 AC: 24560 AN: 215920 AF XY: 0.115

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 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

African (AFR) AF: 0.186 AC: 6001 AN: 32304

American (AMR) AF: 0.0692 AC: 2802 AN: 40512

Ashkenazi Jewish (ASJ) AF: 0.126 AC: 2964 AN: 23456

East Asian (EAS) AF: 0.164 AC: 6420 AN: 39130

South Asian (SAS) AF: 0.153 AC: 12153 AN: 79618

European-Finnish (FIN) AF: 0.0768 AC: 3959 AN: 51570

Middle Eastern (MID) AF: 0.109 AC: 434 AN: 3974

European-Non Finnish (NFE) AF: 0.0952 AC: 103374 AN: 1085660

Other (OTH) AF: 0.118 AC: 6900 AN: 58322

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

African (AFR) AF: 0.178 AC: 7374 AN: 41456

American (AMR) AF: 0.0853 AC: 1305 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.124 AC: 431 AN: 3470

East Asian (EAS) AF: 0.202 AC: 1045 AN: 5170

South Asian (SAS) AF: 0.163 AC: 787 AN: 4818

European-Finnish (FIN) AF: 0.0734 AC: 777 AN: 10582

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0965 AC: 6558 AN: 67988

Other (OTH) AF: 0.107 AC: 227 AN: 2114

Alfa AF: 0.102 Hom.: 1323

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
PhyloP100		-1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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