rs11601507

chr11-5679844-C-Achr11-5679844-C-T

Variant summary

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

The NM_033034.3(TRIM5):c.334G>T(p.Val112Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0767 in 1,613,378 control chromosomes in the GnomAD database, including 5,741 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.063 (415 hom., cov: 31)
  • Exomes 𝑓: 0.078 (5326 hom.)
• Consequence: TRIM5 NM_033034.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.54

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0012705624).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.187 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIM5	NM_033034.3	c.334G>T	p.Val112Phe	missense_variant	2/8	ENST00000380034.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIM5	ENST00000380034.8	c.334G>T	p.Val112Phe	missense_variant	2/8	2	NM_033034.3	P1

Frequencies

GnomAD3 genomes AF: 0.0632 AC: 9573 AN: 151434 Hom.: 417 Cov.: 31

Gnomad AFR AF: 0.0156

Gnomad AMI AF: 0.0549

Gnomad AMR AF: 0.0759

Gnomad ASJ AF: 0.0930

Gnomad EAS AF: 0.0897

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.0798

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0735

Gnomad OTH AF: 0.0804

GnomAD3 exomes AF: 0.0926 AC: 23295 AN: 251454 Hom.: 1430 AF XY: 0.0978 AC XY: 13285 AN XY: 135896

Gnomad AFR exome AF: 0.0129

Gnomad AMR exome AF: 0.108

Gnomad ASJ exome AF: 0.0991

Gnomad EAS exome AF: 0.0861

Gnomad SAS exome AF: 0.186

Gnomad FIN exome AF: 0.0808

Gnomad NFE exome AF: 0.0769

Gnomad OTH exome AF: 0.0915

GnomAD4 exome AF: 0.0781 AC: 114192 AN: 1461826 Hom.: 5326 Cov.: 37 AF XY: 0.0817 AC XY: 59437 AN XY: 727216

Gnomad4 AFR exome AF: 0.0118

Gnomad4 AMR exome AF: 0.105

Gnomad4 ASJ exome AF: 0.0964

Gnomad4 EAS exome AF: 0.0696

Gnomad4 SAS exome AF: 0.183

Gnomad4 FIN exome AF: 0.0798

Gnomad4 NFE exome AF: 0.0703

Gnomad4 OTH exome AF: 0.0824

GnomAD4 genome AF: 0.0631 AC: 9561 AN: 151552 Hom.: 415 Cov.: 31 AF XY: 0.0665 AC XY: 4920 AN XY: 73972

Gnomad4 AFR AF: 0.0155

Gnomad4 AMR AF: 0.0756

Gnomad4 ASJ AF: 0.0930

Gnomad4 EAS AF: 0.0901

Gnomad4 SAS AF: 0.197

Gnomad4 FIN AF: 0.0798

Gnomad4 NFE AF: 0.0735

Gnomad4 OTH AF: 0.0791

Alfa AF: 0.0745 Hom.: 588

Bravo AF: 0.0594

TwinsUK AF: 0.0680 AC: 252

ALSPAC AF: 0.0706 AC: 272

ESP6500AA AF: 0.0164 AC: 72

ESP6500EA AF: 0.0796 AC: 684

ExAC AF: 0.0933 AC: 11325

Asia WGS AF: 0.124 AC: 432 AN: 3478

EpiCase AF: 0.0801

EpiControl AF: 0.0786

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.46
Cadd	Benign	6.4
Dann	Uncertain	0.98
DEOGEN2	Benign	0.034	T;.;.;.
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.037	N
LIST_S2	Uncertain	0.87	D;D;D;D
MetaRNN	Benign	0.0013	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L;L;L;.
MutationTaster	Benign	1.0	N;N;N;N;N;N
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-3.3	D;D;D;D
REVEL	Benign	0.11
Sift	Uncertain	0.025	D;D;D;D
Sift4G	Uncertain	0.010	D;D;D;.
Polyphen		0.53	P;B;P;.
Vest4		0.083
MPC		0.17
ClinPred		0.048	T
GERP RS		-3.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.19
gMVP		0.74

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: rs11601507; hg19: chr11-5701074; COSMIC: COSV59902430; COSMIC: COSV59902430;