1-117115579-A-C

Position:

• chr1-117115579-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_025188.4(TRIM45):​c.1463T>G​(p.Val488Gly) variant causes a missense change involving the alteration of a conserved nucleotide. 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.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TRIM45 NM_025188.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.01

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]

TRIM45 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.815

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM45	NM_025188.4	c.1463T>G	p.Val488Gly	missense_variant	4/6	ENST00000256649.9	NP_079464.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM45	ENST00000256649.9	c.1463T>G	p.Val488Gly	missense_variant	4/6	1	NM_025188.4	ENSP00000256649.4
TRIM45	ENST00000369464.7	c.1409T>G	p.Val470Gly	missense_variant	4/6	1		ENSP00000358476.3
TRIM45	ENST00000369461.3	c.1292T>G	p.Val431Gly	missense_variant	5/7	5		ENSP00000358473.3
TRIM45	ENST00000497970.5	n.32T>G		non_coding_transcript_exon_variant	1/4	5		ENSP00000431261.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 19, 2024

The c.1463T>G (p.V488G) alteration is located in exon 4 (coding exon 4) of the TRIM45 gene. This alteration results from a T to G substitution at nucleotide position 1463, causing the valine (V) at amino acid position 488 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.78
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.070
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.44	T;.;.
Eigen	Uncertain	0.66
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.93	D;D;D
M_CAP	Benign	0.078	D
MetaRNN	Pathogenic	0.82	D;D;D
MetaSVM	Benign	-0.33	T
MutationAssessor	Pathogenic	3.6	H;.;.
PrimateAI	Benign	0.44	T
PROVEAN	Pathogenic	-6.3	D;D;D
REVEL	Uncertain	0.47
Sift	Uncertain	0.0010	D;D;D
Sift4G	Uncertain	0.0020	D;D;D
Polyphen		1.0	D;D;.
Vest4		0.60
MutPred		0.75		Loss of stability (P = 0.0158);.;.;
MVP		0.89
MPC		0.98
ClinPred		1.0	D
GERP RS		4.9
Varity_R		0.97
gMVP		0.86

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-117658201;