rs205498

Variant names:

• chr17-56901433-G-A
• rs205498
• NM_005082.5:c.1073C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-56901433-G-A
• chr17-56901433-G-C
• chr17-56901433-G-T

Variant summary

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

The NM_005082.5(TRIM25):​c.1073C>T​(p.Pro358Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.742 in 1,613,540 control chromosomes in the GnomAD database, including 445,607 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 0.77 (44882 hom., cov: 30)
  • Exomes 𝑓: 0.74 (400725 hom.)
• Consequence: TRIM25 NM_005082.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0170
• Publications: 35 publications found

Genes affected

TRIM25 (HGNC:12932): (tripartite motif containing 25) 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 is an RNA binding protein, functions as a ubiquitin E3 ligase and is involved in multiple cellular processes, including regulation of antiviral innate immunity. [provided by RefSeq, Sep 2021]

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=8.9472604E-7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.812 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005082.5. 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
	TRIM25	NM_005082.5	MANE Select	c.1073C>T	p.Pro358Leu	missense	Exon 4 of 9	NP_005073.2	Q14258

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM25	ENST00000316881.9	TSL:1 MANE Select	c.1073C>T	p.Pro358Leu	missense	Exon 4 of 9	ENSP00000323889.4	Q14258
	TRIM25	ENST00000537230.3	TSL:1	c.1073C>T	p.Pro358Leu	missense	Exon 4 of 10	ENSP00000445961.1	Q14258
	TRIM25	ENST00000572021.6	TSL:1	n.*486C>T		non_coding_transcript_exon	Exon 5 of 10	ENSP00000459980.2	I3L2W4

Frequencies

GnomAD3 genomes AF: 0.767 AC: 116423 AN: 151884 Hom.: 44868 Cov.: 30

Gnomad AFR AF: 0.820

Gnomad AMI AF: 0.669

Gnomad AMR AF: 0.752

Gnomad ASJ AF: 0.863

Gnomad EAS AF: 0.833

Gnomad SAS AF: 0.721

Gnomad FIN AF: 0.738

Gnomad MID AF: 0.820

Gnomad NFE AF: 0.736

Gnomad OTH AF: 0.766

GnomAD2 exomes AF: 0.750 AC: 188477 AN: 251142 AF XY: 0.749

Gnomad AFR exome AF: 0.821

Gnomad AMR exome AF: 0.731

Gnomad ASJ exome AF: 0.854

Gnomad EAS exome AF: 0.830

Gnomad FIN exome AF: 0.744

Gnomad NFE exome AF: 0.732

Gnomad OTH exome AF: 0.760

GnomAD4 exome AF: 0.740 AC: 1081518 AN: 1461538 Hom.: 400725 Cov.: 61 AF XY: 0.740 AC XY: 537932 AN XY: 727078

African (AFR) AF: 0.820 AC: 27446 AN: 33474

American (AMR) AF: 0.728 AC: 32540 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.849 AC: 22172 AN: 26130

East Asian (EAS) AF: 0.816 AC: 32376 AN: 39698

South Asian (SAS) AF: 0.726 AC: 62622 AN: 86238

European-Finnish (FIN) AF: 0.736 AC: 39321 AN: 53408

Middle Eastern (MID) AF: 0.799 AC: 4503 AN: 5638

European-Non Finnish (NFE) AF: 0.733 AC: 815350 AN: 1111882

Other (OTH) AF: 0.749 AC: 45188 AN: 60360

GnomAD4 genome AF: 0.766 AC: 116478 AN: 152002 Hom.: 44882 Cov.: 30 AF XY: 0.767 AC XY: 56957 AN XY: 74288

African (AFR) AF: 0.820 AC: 33981 AN: 41458

American (AMR) AF: 0.752 AC: 11491 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.863 AC: 2995 AN: 3472

East Asian (EAS) AF: 0.832 AC: 4292 AN: 5160

South Asian (SAS) AF: 0.720 AC: 3465 AN: 4812

European-Finnish (FIN) AF: 0.738 AC: 7792 AN: 10552

Middle Eastern (MID) AF: 0.806 AC: 237 AN: 294

European-Non Finnish (NFE) AF: 0.736 AC: 50009 AN: 67964

Other (OTH) AF: 0.765 AC: 1607 AN: 2102

Alfa AF: 0.748 Hom.: 134196

Bravo AF: 0.772

TwinsUK AF: 0.737 AC: 2734

ALSPAC AF: 0.738 AC: 2845

ESP6500AA AF: 0.809 AC: 3565

ESP6500EA AF: 0.739 AC: 6352

ExAC AF: 0.748 AC: 90863

Asia WGS AF: 0.766 AC: 2664 AN: 3478

EpiCase AF: 0.749

EpiControl AF: 0.750

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	11
DANN	Benign	0.71
DEOGEN2	Benign	0.059	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.33	T
MetaRNN	Benign	8.9e-7	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.1	L
PhyloP100		-0.017
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.047
Sift	Benign	0.13	T
Sift4G	Benign	0.092	T
Polyphen		0.050	B
Vest4		0.022
MPC		0.24
ClinPred		0.0050	T
GERP RS		0.60
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.094
gMVP		0.17
Mutation Taster		=97/3	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: rs205498; hg19: chr17-54978794; COSMIC: COSV57545885;