Variant 1-117118339-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_025188.4(TRIM45):c.917A>T(p.Lys306Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

TRIM45
NM_025188.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.21

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM45	NM_025188.4 linkuse as main transcript	c.917A>T	p.Lys306Met	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.917A>T	p.Lys306Met	missense_variant	2/6	1	NM_025188.4	ENSP00000256649	P1	Q9H8W5-1
TRIM45	ENST00000369464.7 linkuse as main transcript	c.917A>T	p.Lys306Met	missense_variant	2/6	1		ENSP00000358476		Q9H8W5-2
TRIM45	ENST00000369461.3 linkuse as main transcript	c.746A>T	p.Lys249Met	missense_variant	3/7	5		ENSP00000358473
TRIM45	ENST00000485032.1 linkuse as main transcript	c.605A>T	p.Lys202Met	missense_variant	3/3	2		ENSP00000474935

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461888

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727244

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

May 24, 2024

The c.917A>T (p.K306M) alteration is located in exon 2 (coding exon 2) of the TRIM45 gene. This alteration results from a A to T substitution at nucleotide position 917, causing the lysine (K) at amino acid position 306 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

0.32

BayesDel_addAF

Uncertain

0.099

BayesDel_noAF

Benign

-0.10

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.040

T;.;.;T

Eigen

Uncertain

0.23

Eigen_PC

Benign

0.15

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.72

T;T;T;T

M_CAP

Uncertain

0.10

MetaRNN

Uncertain

0.58

D;D;D;D

MetaSVM

Uncertain

0.059

MutationAssessor

Uncertain

2.3

M;M;.;.

MutationTaster

Benign

0.96

D;D;D

PrimateAI

Uncertain

0.49

PROVEAN

Pathogenic

-4.6

D;D;D;.

REVEL

Uncertain

0.57

Sift

Uncertain

0.0010

D;D;D;.

Sift4G

Uncertain

0.0040

D;D;D;.

Polyphen

0.99

D;D;.;.

Vest4

0.19

MutPred

0.53

Loss of ubiquitination at K306 (P = 0.0081);Loss of ubiquitination at K306 (P = 0.0081);.;.;

MVP

0.96

MPC

0.93

ClinPred

0.99

GERP RS

3.9

Varity_R

0.34

gMVP

0.66

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over