1-117113380-C-A

Variant names:

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

Variant summary

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

The NM_025188.4(TRIM45):​c.1573G>T​(p.Ala525Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,459,810 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• 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 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.1573G>T	p.Ala525Ser	missense	Exon 5 of 6	NP_079464.2	Q9H8W5-1
	TRIM45	NM_001145635.2		c.1519G>T	p.Ala507Ser	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>T	p.Ala525Ser	missense	Exon 5 of 6	ENSP00000256649.4	Q9H8W5-1
	TRIM45	ENST00000369464.7	TSL:1	c.1519G>T	p.Ala507Ser	missense	Exon 5 of 6	ENSP00000358476.3	Q9H8W5-2
	TRIM45	ENST00000369461.3	TSL:5	c.1402G>T	p.Ala468Ser	missense	Exon 6 of 7	ENSP00000358473.3	Q5T2K3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459810 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726212

African (AFR) AF: 0.00 AC: 0 AN: 33406

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86164

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4230

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111852

Other (OTH) AF: 0.00 AC: 0 AN: 60204

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.040	T
BayesDel_noAF	Benign	-0.18
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0016	T
Eigen	Benign	0.17
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.91	D
M_CAP	Uncertain	0.12	D
MetaRNN	Uncertain	0.51	D
MetaSVM	Uncertain	-0.22	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		7.2
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.33	N
REVEL	Uncertain	0.40
Sift	Uncertain	0.022	D
Sift4G	Uncertain	0.054	T
Polyphen		1.0	D
Vest4		0.44
MutPred		0.47		Loss of loop (P = 0.0804)
MVP		0.88
MPC		0.52
ClinPred		0.95	D
GERP RS		3.9
Varity_R		0.080
gMVP		0.48
Mutation Taster		=69/31	polymorphism

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: rs144861033; hg19: chr1-117656002;