17-56901433-G-C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005082.5(TRIM25):​c.1073C>G​(p.Pro358Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 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: not found (cov: 30)
• Consequence: TRIM25 NM_005082.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0170
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.038874775).

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>G	p.Pro358Arg	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>G	p.Pro358Arg	missense	Exon 4 of 9	ENSP00000323889.4	Q14258
	TRIM25	ENST00000537230.3	TSL:1	c.1073C>G	p.Pro358Arg	missense	Exon 4 of 10	ENSP00000445961.1	Q14258
	TRIM25	ENST00000572021.6	TSL:1	n.*486C>G		non_coding_transcript_exon	Exon 5 of 10	ENSP00000459980.2	I3L2W4

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 61

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	5.5
DANN	Benign	0.20
DEOGEN2	Benign	0.048	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.29	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.039	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.76	N
PhyloP100		-0.017
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.68	N
REVEL	Benign	0.037
Sift	Benign	0.37	T
Sift4G	Benign	0.75	T
Polyphen		0.0	B
Vest4		0.056
MutPred		0.32		Gain of catalytic residue at P358 (P = 0.0112)
MVP		0.25
MPC		0.24
ClinPred		0.038	T
GERP RS		0.60
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.059
gMVP		0.11

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;