rs5030768

Variant names:

• chr11-4390589-T-A
• rs5030768
• NM_003141.4:c.-49-131A>T

Your query was ambiguous. Multiple possible variants found:

• chr11-4390589-T-A
• chr11-4390589-T-C
• chr11-4390589-T-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003141.4(TRIM21):​c.-49-131A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000209 in 478,672 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: TRIM21 NM_003141.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.136
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003141.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM21	NM_003141.4	MANE Select	c.-49-131A>T		intron	N/A	NP_003132.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM21	ENST00000254436.8	TSL:1 MANE Select	c.-49-131A>T		intron	N/A	ENSP00000254436.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000209 AC: 1 AN: 478672 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 244748

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 13418

American (AMR) AF: 0.00 AC: 0 AN: 16590

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13214

East Asian (EAS) AF: 0.00 AC: 0 AN: 30614

South Asian (SAS) AF: 0.00 AC: 0 AN: 33228

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 26960

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1972

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 316264

Other (OTH) AF: 0.0000379 AC: 1 AN: 26412

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	6.8
DANN	Benign	0.92
PhyloP100		-0.14

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: rs5030768; hg19: chr11-4411819;