11-5678261-T-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_033034.3(TRIM5):c.687A>G(p.Arg229=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00441 in 1,614,088 control chromosomes in the GnomAD database, including 293 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.024 (150 hom., cov: 33)
  • Exomes 𝑓: 0.0024 (143 hom.)
• Consequence: TRIM5 NM_033034.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.844

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

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 11-5678261-T-C is Benign according to our data. Variant chr11-5678261-T-C is described in ClinVar as [Benign]. Clinvar id is 783592.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.844 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0803 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIM5	NM_033034.3	c.687A>G	p.Arg229=	synonymous_variant	4/8	ENST00000380034.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIM5	ENST00000380034.8	c.687A>G	p.Arg229=	synonymous_variant	4/8	2	NM_033034.3	P1

Frequencies

GnomAD3 genomes AF: 0.0238 AC: 3622 AN: 152182 Hom.: 150 Cov.: 33

Gnomad AFR AF: 0.0827

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00929

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000309

Gnomad OTH AF: 0.0148

GnomAD3 exomes AF: 0.00617 AC: 1550 AN: 251382 Hom.: 62 AF XY: 0.00445 AC XY: 605 AN XY: 135866

Gnomad AFR exome AF: 0.0849

Gnomad AMR exome AF: 0.00353

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000980

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000237

Gnomad OTH exome AF: 0.00310

GnomAD4 exome AF: 0.00239 AC: 3492 AN: 1461788 Hom.: 143 Cov.: 30 AF XY: 0.00206 AC XY: 1500 AN XY: 727192

Gnomad4 AFR exome AF: 0.0834

Gnomad4 AMR exome AF: 0.00438

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000162

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000143

Gnomad4 OTH exome AF: 0.00525

GnomAD4 genome AF: 0.0238 AC: 3627 AN: 152300 Hom.: 150 Cov.: 33 AF XY: 0.0226 AC XY: 1683 AN XY: 74484

Gnomad4 AFR AF: 0.0826

Gnomad4 AMR AF: 0.00928

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000309

Gnomad4 OTH AF: 0.0147

Alfa AF: 0.0129 Hom.: 39

Bravo AF: 0.0271

Asia WGS AF: 0.00346 AC: 13 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.000415

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Aug 20, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	2.4
Dann	Benign	0.45

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

Publications

LitVar

Other links and lift over

dbSNP: rs58187248; hg19: chr11-5699491;