rs205498

Positions:

• chr17-56901433-G-A

Variant summary

Our verdict is Benign. Variant got -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. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• 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

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]

TRIM25 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM25	NM_005082.5	c.1073C>T	p.Pro358Leu	missense_variant	4/9	ENST00000316881.9	NP_005073.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM25	ENST00000316881.9	c.1073C>T	p.Pro358Leu	missense_variant	4/9	1	NM_005082.5	ENSP00000323889.4

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

GnomAD3 exomes AF: 0.750 AC: 188477 AN: 251142 Hom.: 70930 AF XY: 0.749 AC XY: 101677 AN XY: 135714

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 SAS exome AF: 0.726

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

Gnomad4 AFR exome AF: 0.820

Gnomad4 AMR exome AF: 0.728

Gnomad4 ASJ exome AF: 0.849

Gnomad4 EAS exome AF: 0.816

Gnomad4 SAS exome AF: 0.726

Gnomad4 FIN exome AF: 0.736

Gnomad4 NFE exome AF: 0.733

Gnomad4 OTH exome AF: 0.749

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

Gnomad4 AFR AF: 0.820

Gnomad4 AMR AF: 0.752

Gnomad4 ASJ AF: 0.863

Gnomad4 EAS AF: 0.832

Gnomad4 SAS AF: 0.720

Gnomad4 FIN AF: 0.738

Gnomad4 NFE AF: 0.736

Gnomad4 OTH AF: 0.765

Alfa AF: 0.749 Hom.: 70217

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 v4.3

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;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;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.1	L;L
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.0	N;N
REVEL	Benign	0.047
Sift	Benign	0.13	T;T
Sift4G	Benign	0.092	T;T
Polyphen		0.050	B;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

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: rs205498; hg19: chr17-54978794; COSMIC: COSV57545885;