rs58477024

Variant names:

• chr11-5679851-G-A
• rs58477024
• NM_033034.3:c.327C>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BP7

The NM_033034.3(TRIM5):​c.327C>T​(p.Asp109Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000257 in 1,613,460 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0011 (1 hom., cov: 31)
  • Exomes 𝑓: 0.00017 (0 hom.)
• Consequence: TRIM5 NM_033034.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0410
• Publications: 2 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: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP7: Synonymous conserved (PhyloP=0.041 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033034.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM5	NM_033034.3	MANE Select	c.327C>T	p.Asp109Asp	synonymous	Exon 2 of 8	NP_149023.2	Q9C035-1
	TRIM5	NM_033092.4		c.327C>T	p.Asp109Asp	synonymous	Exon 2 of 7	NP_149083.2	Q9C035-3
	TRIM5	NM_033093.4		c.327C>T	p.Asp109Asp	synonymous	Exon 2 of 8	NP_149084.2	Q9C035-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM5	ENST00000380034.8	TSL:2 MANE Select	c.327C>T	p.Asp109Asp	synonymous	Exon 2 of 8	ENSP00000369373.3	Q9C035-1
	TRIM5	ENST00000396847.7	TSL:1	c.327C>T	p.Asp109Asp	synonymous	Exon 2 of 7	ENSP00000380058.3	Q9C035-3
	TRIM5	ENST00000412903.1	TSL:1	c.327C>T	p.Asp109Asp	synonymous	Exon 3 of 5	ENSP00000388031.1	E7EQQ5

Frequencies

GnomAD3 genomes AF: 0.00112 AC: 169 AN: 151478 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.00388

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000329

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000484

GnomAD2 exomes AF: 0.000326 AC: 82 AN: 251476 AF XY: 0.000250

Gnomad AFR exome AF: 0.00394

Gnomad AMR exome AF: 0.000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000352

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000167 AC: 244 AN: 1461864 Hom.: 0 Cov.: 35 AF XY: 0.000149 AC XY: 108 AN XY: 727232

African (AFR) AF: 0.00433 AC: 145 AN: 33480

American (AMR) AF: 0.000246 AC: 11 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000812 AC: 7 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5768

European-Non Finnish (NFE) AF: 0.0000531 AC: 59 AN: 1111984

Other (OTH) AF: 0.000331 AC: 20 AN: 60396

GnomAD4 genome AF: 0.00112 AC: 170 AN: 151596 Hom.: 1 Cov.: 31 AF XY: 0.00123 AC XY: 91 AN XY: 74032

African (AFR) AF: 0.00390 AC: 161 AN: 41330

American (AMR) AF: 0.000329 AC: 5 AN: 15204

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5114

South Asian (SAS) AF: 0.00 AC: 0 AN: 4752

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10496

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67942

Other (OTH) AF: 0.000479 AC: 1 AN: 2086

Alfa AF: 0.000642 Hom.: 0

Bravo AF: 0.00113

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.000119

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.1
DANN	Benign	0.29
PhyloP100		0.041
PromoterAI		-0.026	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

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: rs58477024; hg19: chr11-5701081; COSMIC: COSV59899406; COSMIC: COSV59899406;