11-5679771-C-T

Variant names:

• chr11-5679771-C-T
• rs10838525
• NM_033034.3:c.407G>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.407G>A​(p.Arg136Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.327 in 1,588,190 control chromosomes in the GnomAD database, including 90,743 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 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 0.28 (6987 hom., cov: 30)
  • Exomes 𝑓: 0.33 (83756 hom.)
• Consequence: TRIM5 NM_033034.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.55
• Publications: 70 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=0.001147449).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.364 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIM5	NM_033034.3	c.407G>A	p.Arg136Gln	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.407G>A	p.Arg136Gln	missense_variant	Exon 2 of 8	2	NM_033034.3	ENSP00000369373.3

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42286 AN: 151118 Hom.: 6993 Cov.: 30

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.312

Gnomad AMR AF: 0.269

Gnomad ASJ AF: 0.301

Gnomad EAS AF: 0.0626

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.426

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.368

Gnomad OTH AF: 0.278

GnomAD2 exomes AF: 0.280 AC: 66584 AN: 237474 AF XY: 0.283

Gnomad AFR exome AF: 0.133

Gnomad AMR exome AF: 0.192

Gnomad ASJ exome AF: 0.310

Gnomad EAS exome AF: 0.0538

Gnomad FIN exome AF: 0.424

Gnomad NFE exome AF: 0.364

Gnomad OTH exome AF: 0.318

GnomAD4 exome AF: 0.332 AC: 476888 AN: 1436954 Hom.: 83756 Cov.: 35 AF XY: 0.328 AC XY: 233627 AN XY: 712178

African (AFR) AF: 0.131 AC: 4326 AN: 33100

American (AMR) AF: 0.201 AC: 8663 AN: 43174

Ashkenazi Jewish (ASJ) AF: 0.304 AC: 7447 AN: 24476

East Asian (EAS) AF: 0.0728 AC: 2870 AN: 39418

South Asian (SAS) AF: 0.175 AC: 14499 AN: 82788

European-Finnish (FIN) AF: 0.424 AC: 22186 AN: 52302

Middle Eastern (MID) AF: 0.281 AC: 1577 AN: 5616

European-Non Finnish (NFE) AF: 0.362 AC: 397039 AN: 1096760

Other (OTH) AF: 0.308 AC: 18281 AN: 59320

GnomAD4 genome AF: 0.280 AC: 42281 AN: 151236 Hom.: 6987 Cov.: 30 AF XY: 0.277 AC XY: 20469 AN XY: 73778

African (AFR) AF: 0.139 AC: 5739 AN: 41286

American (AMR) AF: 0.269 AC: 4070 AN: 15146

Ashkenazi Jewish (ASJ) AF: 0.301 AC: 1041 AN: 3464

East Asian (EAS) AF: 0.0630 AC: 323 AN: 5128

South Asian (SAS) AF: 0.162 AC: 763 AN: 4710

European-Finnish (FIN) AF: 0.426 AC: 4414 AN: 10372

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.368 AC: 24982 AN: 67848

Other (OTH) AF: 0.277 AC: 577 AN: 2082

Alfa AF: 0.330 Hom.: 38501

Bravo AF: 0.259

TwinsUK AF: 0.373 AC: 1384

ALSPAC AF: 0.353 AC: 1362

ESP6500AA AF: 0.144 AC: 633

ESP6500EA AF: 0.350 AC: 3012

ExAC AF: 0.280 AC: 33925

Asia WGS AF: 0.169 AC: 586 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	7.2
DANN	Benign	0.21
DEOGEN2	Benign	0.00033	T;.;.;.
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0033	N
LIST_S2	Benign	0.14	T;T;T;T
MetaRNN	Benign	0.0011	T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-1.8	N;N;N;.
PhyloP100		1.5
PrimateAI	Benign	0.22	T
PROVEAN	Benign	1.8	N;N;N;N
REVEL	Benign	0.10
Sift	Benign	1.0	T;T;T;T
Sift4G	Benign	1.0	T;T;T;.
Polyphen		0.0	B;B;B;.
Vest4		0.018
MPC		0.058
ClinPred		0.00083	T
GERP RS		0.20
PromoterAI		0.0024	Neutral
Varity_R		0.014
gMVP		0.10
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10838525; hg19: chr11-5701001; COSMIC: COSV59899089; COSMIC: COSV59899089;