11-5680051-G-A

Position:

• chr11-5680051-G-A

Variant summary

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

The NM_033034.3(TRIM5):​c.127C>T​(p.His43Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 1,613,938 control chromosomes in the GnomAD database, including 12,925 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 0.11 (988 hom., cov: 32)
  • Exomes 𝑓: 0.13 (11937 hom.)
• Consequence: TRIM5 NM_033034.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.75

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]

TRIM5 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0018083751).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM5	NM_033034.3	c.127C>T	p.His43Tyr	missense_variant	2/8	ENST00000380034.8	NP_149023.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM5	ENST00000380034.8	c.127C>T	p.His43Tyr	missense_variant	2/8	2	NM_033034.3	ENSP00000369373.3

Frequencies

GnomAD3 genomes AF: 0.107 AC: 16191 AN: 151986 Hom.: 987 Cov.: 32

Gnomad AFR AF: 0.0601

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.132

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.161

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.119

Gnomad OTH AF: 0.113

GnomAD3 exomes AF: 0.126 AC: 31707 AN: 251462 Hom.: 2232 AF XY: 0.125 AC XY: 17042 AN XY: 135904

Gnomad AFR exome AF: 0.0558

Gnomad AMR exome AF: 0.160

Gnomad ASJ exome AF: 0.139

Gnomad EAS exome AF: 0.171

Gnomad SAS exome AF: 0.129

Gnomad FIN exome AF: 0.118

Gnomad NFE exome AF: 0.118

Gnomad OTH exome AF: 0.118

GnomAD4 exome AF: 0.125 AC: 182840 AN: 1461834 Hom.: 11937 Cov.: 58 AF XY: 0.125 AC XY: 90766 AN XY: 727220

Gnomad4 AFR exome AF: 0.0560

Gnomad4 AMR exome AF: 0.157

Gnomad4 ASJ exome AF: 0.142

Gnomad4 EAS exome AF: 0.173

Gnomad4 SAS exome AF: 0.129

Gnomad4 FIN exome AF: 0.117

Gnomad4 NFE exome AF: 0.124

Gnomad4 OTH exome AF: 0.121

GnomAD4 genome AF: 0.107 AC: 16205 AN: 152104 Hom.: 988 Cov.: 32 AF XY: 0.108 AC XY: 8005 AN XY: 74352

Gnomad4 AFR AF: 0.0600

Gnomad4 AMR AF: 0.133

Gnomad4 ASJ AF: 0.136

Gnomad4 EAS AF: 0.160

Gnomad4 SAS AF: 0.122

Gnomad4 FIN AF: 0.117

Gnomad4 NFE AF: 0.119

Gnomad4 OTH AF: 0.116

Alfa AF: 0.119 Hom.: 2140

Bravo AF: 0.106

TwinsUK AF: 0.127 AC: 472

ALSPAC AF: 0.122 AC: 472

ESP6500AA AF: 0.0602 AC: 265

ESP6500EA AF: 0.121 AC: 1038

ExAC AF: 0.123 AC: 14926

Asia WGS AF: 0.128 AC: 443 AN: 3478

EpiCase AF: 0.115

EpiControl AF: 0.121

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	3.6
DANN	Benign	0.22
DEOGEN2	Benign	0.016	T;.;.;.;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0074	N
LIST_S2	Benign	0.064	T;T;T;T;T
MetaRNN	Benign	0.0018	T;T;T;T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	-0.98	N;N;N;.;.
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.6	N;N;N;N;N
REVEL	Benign	0.21
Sift	Benign	1.0	T;T;T;T;T
Sift4G	Benign	1.0	T;T;T;.;T
Polyphen		0.099	B;B;B;.;.
Vest4		0.028
MPC		0.063
ClinPred		0.012	T
GERP RS		0.29
Varity_R		0.029
gMVP		0.35

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs3740996; hg19: chr11-5701281; COSMIC: COSV59899015; COSMIC: COSV59899015;