11-5679419-A-G

Variant names:

• chr11-5679419-A-G
• rs10769175
• NM_033034.3:c.418-250T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033034.3(TRIM5):​c.418-250T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.662 in 151,860 control chromosomes in the GnomAD database, including 35,341 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 0.66 (35341 hom., cov: 30)
• Consequence: TRIM5 NM_033034.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.53
• Publications: 8 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.787 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIM5	NM_033034.3	c.418-250T>C		intron_variant	Intron 2 of 7	ENST00000380034.8	NP_149023.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIM5	ENST00000380034.8	c.418-250T>C		intron_variant	Intron 2 of 7	2	NM_033034.3	ENSP00000369373.3

Frequencies

GnomAD3 genomes AF: 0.662 AC: 100480 AN: 151744 Hom.: 35346 Cov.: 30

Gnomad AFR AF: 0.445

Gnomad AMI AF: 0.784

Gnomad AMR AF: 0.615

Gnomad ASJ AF: 0.760

Gnomad EAS AF: 0.392

Gnomad SAS AF: 0.683

Gnomad FIN AF: 0.814

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.792

Gnomad OTH AF: 0.688

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.662 AC: 100509 AN: 151860 Hom.: 35341 Cov.: 30 AF XY: 0.660 AC XY: 49014 AN XY: 74230

African (AFR) AF: 0.445 AC: 18413 AN: 41366

American (AMR) AF: 0.614 AC: 9377 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.760 AC: 2638 AN: 3470

East Asian (EAS) AF: 0.392 AC: 2012 AN: 5134

South Asian (SAS) AF: 0.683 AC: 3286 AN: 4812

European-Finnish (FIN) AF: 0.814 AC: 8595 AN: 10560

Middle Eastern (MID) AF: 0.707 AC: 208 AN: 294

European-Non Finnish (NFE) AF: 0.792 AC: 53824 AN: 67936

Other (OTH) AF: 0.685 AC: 1444 AN: 2108

Alfa AF: 0.752 Hom.: 70949

Bravo AF: 0.634

Asia WGS AF: 0.528 AC: 1840 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.56
DANN	Benign	0.57
PhyloP100		-2.5
PromoterAI		0.024	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10769175; hg19: chr11-5700649;