NM_005082.5:c.1363+303C>T

Variant names:

• chr17-56895040-G-A
• rs205499
• NM_005082.5:c.1363+303C>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.1363+303C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 152,164 control chromosomes in the GnomAD database, including 2,599 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 0.18 (2599 hom., cov: 32)
• Consequence: TRIM25 NM_005082.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.348
• Publications: 10 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 (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.195 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIM25	NM_005082.5	c.1363+303C>T		intron_variant	Intron 8 of 8	ENST00000316881.9	NP_005073.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIM25	ENST00000316881.9	c.1363+303C>T		intron_variant	Intron 8 of 8	1	NM_005082.5	ENSP00000323889.4

Frequencies

GnomAD3 genomes AF: 0.179 AC: 27249 AN: 152048 Hom.: 2603 Cov.: 32

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.301

Gnomad AMR AF: 0.181

Gnomad ASJ AF: 0.246

Gnomad EAS AF: 0.0129

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.218

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.198

Gnomad OTH AF: 0.198

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.179 AC: 27240 AN: 152164 Hom.: 2599 Cov.: 32 AF XY: 0.176 AC XY: 13107 AN XY: 74392

African (AFR) AF: 0.156 AC: 6461 AN: 41516

American (AMR) AF: 0.181 AC: 2770 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.246 AC: 853 AN: 3470

East Asian (EAS) AF: 0.0125 AC: 65 AN: 5188

South Asian (SAS) AF: 0.121 AC: 581 AN: 4812

European-Finnish (FIN) AF: 0.218 AC: 2315 AN: 10596

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.198 AC: 13453 AN: 67982

Other (OTH) AF: 0.196 AC: 413 AN: 2108

Alfa AF: 0.194 Hom.: 6469

Bravo AF: 0.177

Asia WGS AF: 0.0660 AC: 233 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.3
DANN	Benign	0.62
PhyloP100		-0.35
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs205499; hg19: chr17-54972401;