Variant 1-117118448-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_025188.4(TRIM45):c.808G>A(p.Val270Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000239 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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)

Exomes 𝑓: 0.000024 ( 0 hom. )

Consequence

TRIM45
NM_025188.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.71

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.2878994).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM45	NM_025188.4 linkuse as main transcript	c.808G>A	p.Val270Met	missense_variant	2/6	ENST00000256649.9	NP_079464.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM45	ENST00000256649.9 linkuse as main transcript	c.808G>A	p.Val270Met	missense_variant	2/6	1	NM_025188.4	ENSP00000256649	P1	Q9H8W5-1
TRIM45	ENST00000369464.7 linkuse as main transcript	c.808G>A	p.Val270Met	missense_variant	2/6	1		ENSP00000358476		Q9H8W5-2
TRIM45	ENST00000369461.3 linkuse as main transcript	c.637G>A	p.Val213Met	missense_variant	3/7	5		ENSP00000358473
TRIM45	ENST00000485032.1 linkuse as main transcript	c.496G>A	p.Val166Met	missense_variant	3/3	2		ENSP00000474935

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000199

AC:

AN:

251480

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135912

show subpopulations

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000440

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000239

AC:

AN:

1461892

Hom.:

Cov.:

AF XY:

0.0000206

AC XY:

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000315

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 13, 2022

The c.808G>A (p.V270M) alteration is located in exon 2 (coding exon 2) of the TRIM45 gene. This alteration results from a G to A substitution at nucleotide position 808, causing the valine (V) at amino acid position 270 to be replaced by a methionine (M). 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

0.12

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.29

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0032

T;.;.;T

Eigen

Benign

0.097

Eigen_PC

Benign

0.17

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.89

D;D;D;D

M_CAP

Benign

0.029

MetaRNN

Benign

0.29

T;T;T;T

MetaSVM

Benign

-0.48

MutationAssessor

Benign

0.85

L;L;.;.

MutationTaster

Benign

0.72

D;D;D

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.37

N;N;N;.

REVEL

Benign

0.24

Sift

Benign

0.091

T;T;T;.

Sift4G

Benign

0.083

T;T;T;.

Polyphen

0.75

P;P;.;.

Vest4

0.12

MutPred

0.48

Loss of helix (P = 0.0068);Loss of helix (P = 0.0068);.;.;

MVP

0.93

MPC

0.34

ClinPred

0.30

GERP RS

4.3

Varity_R

0.092

gMVP

0.46

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over