rs3858526

Positions:

• chr11-5938527-A-C
• chr11-5938527-A-T

Variant summary

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

The ENST00000412903.1(TRIM5):​c.-334T>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 151,896 control chromosomes in the GnomAD database, including 7,431 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 0.30 (7431 hom., cov: 31)
  • Exomes 𝑓: 0.25 (0 hom.)
• Consequence: TRIM5 ENST00000412903.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.20

Genes affected

TRIM5 (HGNC:16276): (tripartite motif containing 5) The protein encoded by this gene is 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 protein forms homo-oligomers via the coilel-coil region and localizes to cytoplasmic bodies. It appears to function as a E3 ubiquitin-ligase and ubiqutinates itself to regulate its subcellular localization. It may play a role in retroviral restriction. Multiple alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Dec 2009]

LOC112268071 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.397 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC112268071	XR_002957230.2	n.95T>G		non_coding_transcript_exon_variant	1/3
LOC112268071	XR_002957231.2	n.95T>G		non_coding_transcript_exon_variant	1/3
LOC112268071	XR_002957234.2	n.95T>G		non_coding_transcript_exon_variant	1/3
LOC112268071	XR_007062562.1	n.95T>G		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM5	ENST00000412903.1	c.-334T>G		5_prime_UTR_variant	1/5	1		ENSP00000388031.1

Frequencies

GnomAD3 genomes AF: 0.304 AC: 46178 AN: 151766 Hom.: 7413 Cov.: 31

Gnomad AFR AF: 0.402

Gnomad AMI AF: 0.220

Gnomad AMR AF: 0.290

Gnomad ASJ AF: 0.232

Gnomad EAS AF: 0.245

Gnomad SAS AF: 0.243

Gnomad FIN AF: 0.292

Gnomad MID AF: 0.264

Gnomad NFE AF: 0.264

Gnomad OTH AF: 0.291

GnomAD4 exome AF: 0.250 AC: 3 AN: 12 Hom.: 0 Cov.: 0 AF XY: 0.200 AC XY: 2 AN XY: 10

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.200

GnomAD4 genome AF: 0.304 AC: 46240 AN: 151884 Hom.: 7431 Cov.: 31 AF XY: 0.303 AC XY: 22464 AN XY: 74218

Gnomad4 AFR AF: 0.402

Gnomad4 AMR AF: 0.290

Gnomad4 ASJ AF: 0.232

Gnomad4 EAS AF: 0.246

Gnomad4 SAS AF: 0.241

Gnomad4 FIN AF: 0.292

Gnomad4 NFE AF: 0.264

Gnomad4 OTH AF: 0.294

Alfa AF: 0.265 Hom.: 7058

Bravo AF: 0.308

Asia WGS AF: 0.264 AC: 918 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.9
DANN	Benign	0.55

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3858526; hg19: chr11-5959757;