chr11-5667710-C-T

Variant names:

• chr11-5667710-C-T
• rs11038628
• NM_033034.3:c.746G>A

Variant summary

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

The NM_033034.3(TRIM5):​c.746G>A​(p.Gly249Asp) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0917 in 1,611,612 control chromosomes in the GnomAD database, including 12,698 homozygotes. In-silico tool predicts a benign outcome for this variant. 17/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.14 (2459 hom., cov: 32)
  • Exomes 𝑓: 0.086 (10239 hom.)
• Consequence: TRIM5 NM_033034.3 missense, splice_region
• Scores: Splicing: ADA: 0.00001234
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.145
• Publications: 42 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]

ENSG00000239920 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.0012489855).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.416 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIM5	NM_033034.3	c.746G>A	p.Gly249Asp	missense_variant, splice_region_variant	Exon 5 of 8	ENST00000380034.8	NP_149023.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIM5	ENST00000380034.8	c.746G>A	p.Gly249Asp	missense_variant, splice_region_variant	Exon 5 of 8	2	NM_033034.3	ENSP00000369373.3
ENSG00000239920	ENST00000380259.7	n.231+10494G>A		intron_variant	Intron 1 of 7	5		ENSP00000369609.3

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21868 AN: 151932 Hom.: 2457 Cov.: 32

Gnomad AFR AF: 0.254

Gnomad AMI AF: 0.0417

Gnomad AMR AF: 0.214

Gnomad ASJ AF: 0.0543

Gnomad EAS AF: 0.430

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.0590

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0577

Gnomad OTH AF: 0.132

GnomAD2 exomes AF: 0.143 AC: 35854 AN: 250190 AF XY: 0.133

Gnomad AFR exome AF: 0.265

Gnomad AMR exome AF: 0.289

Gnomad ASJ exome AF: 0.0494

Gnomad EAS exome AF: 0.444

Gnomad FIN exome AF: 0.0590

Gnomad NFE exome AF: 0.0579

Gnomad OTH exome AF: 0.115

GnomAD4 exome AF: 0.0862 AC: 125813 AN: 1459562 Hom.: 10239 Cov.: 30 AF XY: 0.0864 AC XY: 62707 AN XY: 726164

African (AFR) AF: 0.262 AC: 8737 AN: 33288

American (AMR) AF: 0.278 AC: 12319 AN: 44384

Ashkenazi Jewish (ASJ) AF: 0.0531 AC: 1384 AN: 26086

East Asian (EAS) AF: 0.421 AC: 16619 AN: 39484

South Asian (SAS) AF: 0.148 AC: 12739 AN: 85978

European-Finnish (FIN) AF: 0.0588 AC: 3136 AN: 53368

Middle Eastern (MID) AF: 0.0847 AC: 488 AN: 5764

European-Non Finnish (NFE) AF: 0.0573 AC: 63704 AN: 1110942

Other (OTH) AF: 0.111 AC: 6687 AN: 60268

GnomAD4 genome AF: 0.144 AC: 21905 AN: 152050 Hom.: 2459 Cov.: 32 AF XY: 0.147 AC XY: 10966 AN XY: 74346

African (AFR) AF: 0.254 AC: 10534 AN: 41414

American (AMR) AF: 0.214 AC: 3271 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0543 AC: 188 AN: 3464

East Asian (EAS) AF: 0.431 AC: 2225 AN: 5166

South Asian (SAS) AF: 0.164 AC: 788 AN: 4812

European-Finnish (FIN) AF: 0.0590 AC: 625 AN: 10596

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0578 AC: 3930 AN: 68010

Other (OTH) AF: 0.133 AC: 279 AN: 2104

Alfa AF: 0.0930 Hom.: 5722

Bravo AF: 0.166

TwinsUK AF: 0.0499 AC: 185

ALSPAC AF: 0.0623 AC: 240

ESP6500AA AF: 0.255 AC: 1122

ESP6500EA AF: 0.0584 AC: 502

ExAC AF: 0.141 AC: 17136

Asia WGS AF: 0.300 AC: 1040 AN: 3478

EpiCase AF: 0.0570

EpiControl AF: 0.0570

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	3.8
DANN	Benign	0.086
DEOGEN2	Benign	0.00012	T;.;.
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.0030	N
LIST_S2	Benign	0.58	T;T;T
MetaRNN	Benign	0.0012	T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.61	N;N;N
PhyloP100		-0.14
PrimateAI	Benign	0.26	T
PROVEAN	Benign	4.0	N;N;N
REVEL	Benign	0.12
Sift	Benign	1.0	T;T;T
Sift4G	Benign	1.0	T;T;T
Polyphen		0.0	B;B;B
Vest4		0.040
MPC		0.064
ClinPred		0.00059	T
GERP RS		1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.062
gMVP		0.15
Mutation Taster		=91/9	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000012
dbscSNV1_RF	Benign	0.0020
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

Other links and lift over

dbSNP: rs11038628; hg19: chr11-5688940; COSMIC: COSV59899319;