1-117115607-C-A

Variant names:

• chr1-117115607-C-A
• rs149166047
• NM_025188.4:c.1435G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_025188.4(TRIM45):​c.1435G>T​(p.Val479Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. V479M) 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: 4.01
• Publications: 5 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.1435G>T	p.Val479Leu	missense	Exon 4 of 6	NP_079464.2	Q9H8W5-1
	TRIM45	NM_001145635.2		c.1381G>T	p.Val461Leu	missense	Exon 4 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.1435G>T	p.Val479Leu	missense	Exon 4 of 6	ENSP00000256649.4	Q9H8W5-1
	TRIM45	ENST00000369464.7	TSL:1	c.1381G>T	p.Val461Leu	missense	Exon 4 of 6	ENSP00000358476.3	Q9H8W5-2
	TRIM45	ENST00000369461.3	TSL:5	c.1264G>T	p.Val422Leu	missense	Exon 5 of 7	ENSP00000358473.3	Q5T2K3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Benign	23
DANN	Benign	0.97
DEOGEN2	Benign	0.026	T
Eigen	Benign	0.073
Eigen_PC	Benign	0.11
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.020	T
MetaRNN	Uncertain	0.71	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L
PhyloP100		4.0
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.15	N
REVEL	Benign	0.23
Sift	Benign	0.15	T
Sift4G	Benign	0.18	T
Polyphen		0.77	P
Vest4		0.69
MutPred		0.61		Loss of sheet (P = 0.0126)
MVP		0.59
MPC		0.26
ClinPred		0.46	T
GERP RS		4.9
Varity_R		0.20
gMVP		0.48
Mutation Taster		=43/57	disease causing

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: rs149166047; hg19: chr1-117658229;