rs11601507

Variant names:

• chr11-5679844-C-A
• rs11601507
• NM_033034.3:c.334G>T

Your query was ambiguous. Multiple possible variants found:

• chr11-5679844-C-A
• chr11-5679844-C-G
• chr11-5679844-C-T

Variant summary

Our verdict is Benign. The variant received -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. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 67 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 (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 rank	MANE	Protein	UniProt
TRIM5	NM_033034.3	c.334G>T	p.Val112Phe	missense_variant	Exon 2 of 8	ENST00000380034.8	NP_149023.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIM5	ENST00000380034.8	c.334G>T	p.Val112Phe	missense_variant	Exon 2 of 8	2	NM_033034.3	ENSP00000369373.3

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

GnomAD2 exomes AF: 0.0926 AC: 23295 AN: 251454 AF XY: 0.0978

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 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

African (AFR) AF: 0.0118 AC: 394 AN: 33480

American (AMR) AF: 0.105 AC: 4693 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0964 AC: 2520 AN: 26134

East Asian (EAS) AF: 0.0696 AC: 2764 AN: 39700

South Asian (SAS) AF: 0.183 AC: 15797 AN: 86254

European-Finnish (FIN) AF: 0.0798 AC: 4265 AN: 53420

Middle Eastern (MID) AF: 0.0978 AC: 564 AN: 5768

European-Non Finnish (NFE) AF: 0.0703 AC: 78219 AN: 1111954

Other (OTH) AF: 0.0824 AC: 4976 AN: 60394

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

African (AFR) AF: 0.0155 AC: 642 AN: 41364

American (AMR) AF: 0.0756 AC: 1150 AN: 15204

Ashkenazi Jewish (ASJ) AF: 0.0930 AC: 322 AN: 3464

East Asian (EAS) AF: 0.0901 AC: 458 AN: 5084

South Asian (SAS) AF: 0.197 AC: 929 AN: 4712

European-Finnish (FIN) AF: 0.0798 AC: 839 AN: 10508

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0735 AC: 4991 AN: 67926

Other (OTH) AF: 0.0791 AC: 165 AN: 2086

Alfa AF: 0.0705 Hom.: 812

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;.
PhyloP100		-4.5
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
PromoterAI		0.021	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.19
gMVP		0.74
Mutation Taster		=99/1	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: rs11601507; hg19: chr11-5701074; COSMIC: COSV59902430; COSMIC: COSV59902430;