1-117113380-C-G

Variant names:

• chr1-117113380-C-G
• rs144861033
• NM_025188.4:c.1573G>C

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_025188.4(TRIM45):​c.1573G>C​(p.Ala525Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A525T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TRIM45 NM_025188.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.17
• Publications: 0 publications found

Genes affected

TRIM45 (HGNC:19018): (tripartite motif containing 45) Predicted to enable ubiquitin-protein transferase activity. Predicted to be involved in positive regulation of transcription, DNA-templated. Predicted to act upstream of or within bone development. Located in cytosol; intercellular bridge; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.855

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025188.4. 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
	TRIM45	NM_025188.4	MANE Select	c.1573G>C	p.Ala525Pro	missense	Exon 5 of 6	NP_079464.2	Q9H8W5-1
	TRIM45	NM_001145635.2		c.1519G>C	p.Ala507Pro	missense	Exon 5 of 6	NP_001139107.1	Q9H8W5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM45	ENST00000256649.9	TSL:1 MANE Select	c.1573G>C	p.Ala525Pro	missense	Exon 5 of 6	ENSP00000256649.4	Q9H8W5-1
	TRIM45	ENST00000369464.7	TSL:1	c.1519G>C	p.Ala507Pro	missense	Exon 5 of 6	ENSP00000358476.3	Q9H8W5-2
	TRIM45	ENST00000369461.3	TSL:5	c.1402G>C	p.Ala468Pro	missense	Exon 6 of 7	ENSP00000358473.3	Q5T2K3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.47
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.040
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.032	T
Eigen	Uncertain	0.29
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.93	D
M_CAP	Uncertain	0.19	D
MetaRNN	Pathogenic	0.86	D
MetaSVM	Uncertain	0.099	D
MutationAssessor	Uncertain	2.2	M
PhyloP100		7.2
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-1.8	N
REVEL	Uncertain	0.62
Sift	Uncertain	0.011	D
Sift4G	Uncertain	0.026	D
Polyphen		1.0	D
Vest4		0.67
MutPred		0.52		Gain of methylation at K520 (P = 0.079)
MVP		0.95
MPC		0.98
ClinPred		0.98	D
GERP RS		3.9
Varity_R		0.33
gMVP		0.84
Mutation Taster		=40/60	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs144861033; hg19: chr1-117656002;