11-5664855-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_033034.3(TRIM5):c.1436C>T(p.Pro479Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00156 in 1,611,572 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.0085 (14 hom., cov: 32)
  • Exomes 𝑓: 0.00084 (15 hom.)
• Consequence: TRIM5 NM_033034.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.572

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0040875673).
• BP6: Variant 11-5664855-G-A is Benign according to our data. Variant chr11-5664855-G-A is described in ClinVar as [Benign]. Clinvar id is 768421.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00845 (1286/152122) while in subpopulation AFR AF= 0.0273 (1131/41496). AF 95% confidence interval is 0.0259. There are 14 homozygotes in gnomad4. There are 615 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 14 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIM5	NM_033034.3	c.1436C>T	p.Pro479Leu	missense_variant	8/8	ENST00000380034.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIM5	ENST00000380034.8	c.1436C>T	p.Pro479Leu	missense_variant	8/8	2	NM_033034.3	P1

Frequencies

GnomAD3 genomes AF: 0.00847 AC: 1287 AN: 152004 Hom.: 14 Cov.: 32

Gnomad AFR AF: 0.0273

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00845

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000830

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00720

GnomAD3 exomes AF: 0.00232 AC: 577 AN: 248628 Hom.: 7 AF XY: 0.00183 AC XY: 246 AN XY: 134414

Gnomad AFR exome AF: 0.0304

Gnomad AMR exome AF: 0.00161

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000124

Gnomad OTH exome AF: 0.00248

GnomAD4 exome AF: 0.000843 AC: 1230 AN: 1459450 Hom.: 15 Cov.: 34 AF XY: 0.000737 AC XY: 535 AN XY: 726018

Gnomad4 AFR exome AF: 0.0272

Gnomad4 AMR exome AF: 0.00223

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000349

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000621

Gnomad4 OTH exome AF: 0.00244

GnomAD4 genome AF: 0.00845 AC: 1286 AN: 152122 Hom.: 14 Cov.: 32 AF XY: 0.00827 AC XY: 615 AN XY: 74354

Gnomad4 AFR AF: 0.0273

Gnomad4 AMR AF: 0.00844

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000623

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.00713

Alfa AF: 0.00181 Hom.: 10

Bravo AF: 0.0105

ESP6500AA AF: 0.0302 AC: 133

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00283 AC: 344

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Aug 20, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.44
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.43
Cadd	Benign	17
Dann	Uncertain	0.99
DEOGEN2	Benign	0.044	T
Eigen	Benign	-0.034
Eigen_PC	Benign	-0.23
FATHMM_MKL	Benign	0.38	N
LIST_S2	Benign	0.83	T
MetaRNN	Benign	0.0041	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.8	L
MutationTaster	Benign	1.0	N;N;N;N;N;N
PrimateAI	Benign	0.28	T
PROVEAN	Pathogenic	-8.3	D
REVEL	Benign	0.15
Sift	Uncertain	0.012	D
Sift4G	Uncertain	0.019	D
Polyphen		1.0	D
Vest4		0.10
MVP		0.82
MPC		0.19
ClinPred		0.13	T
GERP RS		2.4
Varity_R		0.16
gMVP		0.43

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: rs7104422; hg19: chr11-5686085;