1-117113445-G-A

Position:

• chr1-117113445-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_025188.4(TRIM45):​c.1508C>T​(p.Pro503Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TRIM45 NM_025188.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.50

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39059436).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM45	NM_025188.4	c.1508C>T	p.Pro503Leu	missense_variant	5/6	ENST00000256649.9	NP_079464.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM45	ENST00000256649.9	c.1508C>T	p.Pro503Leu	missense_variant	5/6	1	NM_025188.4	ENSP00000256649	P1
TRIM45	ENST00000369464.7	c.1454C>T	p.Pro485Leu	missense_variant	5/6	1		ENSP00000358476
TRIM45	ENST00000369461.3	c.1337C>T	p.Pro446Leu	missense_variant	6/7	5		ENSP00000358473
TRIM45	ENST00000497970.5	c.80C>T	p.Pro27Leu	missense_variant, NMD_transcript_variant	2/4	5		ENSP00000431261

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

Dec 27, 2022

The c.1508C>T (p.P503L) alteration is located in exon 5 (coding exon 5) of the TRIM45 gene. This alteration results from a C to T substitution at nucleotide position 1508, causing the proline (P) at amino acid position 503 to be replaced by a leucine (L). 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	Benign	0.080
BayesDel_addAF	Benign	0.011	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.041	T;.;.
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.13
FATHMM_MKL	Benign	0.18	N
LIST_S2	Uncertain	0.90	D;D;D
M_CAP	Benign	0.040	D
MetaRNN	Benign	0.39	T;T;T
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	1.7	L;.;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.27	T
PROVEAN	Uncertain	-2.9	D;D;D
REVEL	Benign	0.20
Sift	Benign	0.064	T;T;D
Sift4G	Benign	0.25	T;T;T
Polyphen		0.21	B;B;.
Vest4		0.24
MutPred		0.56		Loss of sheet (P = 0.0084);.;.;
MVP		0.91
MPC		0.28
ClinPred		0.30	T
GERP RS		4.0
Varity_R		0.040
gMVP		0.24

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: chr1-117656067;