chr1-117113385-C-A

Variant names:

• chr1-117113385-C-A
• rs199984487
• NM_025188.4:c.1568G>T

Variant summary

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

The NM_025188.4(TRIM45):​c.1568G>T​(p.Arg523Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000844 in 1,612,082 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R523C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000091 (0 hom.)
• Consequence: TRIM45 NM_025188.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.51
• 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 0 ACMG points.

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.1568G>T	p.Arg523Leu	missense	Exon 5 of 6	NP_079464.2	Q9H8W5-1
	TRIM45	NM_001145635.2		c.1514G>T	p.Arg505Leu	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.1568G>T	p.Arg523Leu	missense	Exon 5 of 6	ENSP00000256649.4	Q9H8W5-1
	TRIM45	ENST00000369464.7	TSL:1	c.1514G>T	p.Arg505Leu	missense	Exon 5 of 6	ENSP00000358476.3	Q9H8W5-2
	TRIM45	ENST00000369461.3	TSL:5	c.1397G>T	p.Arg466Leu	missense	Exon 6 of 7	ENSP00000358473.3	Q5T2K3

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152240 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000239 AC: 6 AN: 251168 AF XY: 0.0000221

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000529

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000911 AC: 133 AN: 1459842 Hom.: 0 Cov.: 30 AF XY: 0.0000909 AC XY: 66 AN XY: 726232

African (AFR) AF: 0.0000299 AC: 1 AN: 33408

American (AMR) AF: 0.00 AC: 0 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

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: 53398

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4244

European-Non Finnish (NFE) AF: 0.000119 AC: 132 AN: 1111868

Other (OTH) AF: 0.00 AC: 0 AN: 60214

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152240 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74378

African (AFR) AF: 0.00 AC: 0 AN: 41460

American (AMR) AF: 0.00 AC: 0 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5204

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68042

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000987 Hom.: 0

Bravo AF: 0.0000529

ExAC AF: 0.0000165 AC: 2

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.047	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0075	T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.21
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.90	D
M_CAP	Uncertain	0.11	D
MetaRNN	Uncertain	0.48	T
MetaSVM	Benign	-0.70	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		3.5
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.94	N
REVEL	Uncertain	0.32
Sift	Benign	0.083	T
Sift4G	Benign	0.16	T
Polyphen		0.094	B
Vest4		0.53
MVP		0.87
MPC		0.30
ClinPred		0.23	T
GERP RS		3.9
Varity_R		0.15
gMVP		0.63
Mutation Taster		=31/69	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: rs199984487; hg19: chr1-117656007;