2-95594418-C-T

Variant summary

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

The NM_138800.3(TRIM43):​c.395C>T​(p.Ala132Val) 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 30)

Consequence

TRIM43
NM_138800.3 missense

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.124
Variant links:
Genes affected
TRIM43 (HGNC:19015): (tripartite motif containing 43) Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in innate immune response; protein ubiquitination; and regulation of gene expression. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

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
TRIM43NM_138800.3 linkc.395C>T p.Ala132Val missense_variant 2/7 ENST00000272395.3 NP_620155.1 Q96BQ3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TRIM43ENST00000272395.3 linkc.395C>T p.Ala132Val missense_variant 2/71 NM_138800.3 ENSP00000272395.2 Q96BQ3

Frequencies

GnomAD3 genomes
Cov.:
30
GnomAD4 exome
Cov.:
33
GnomAD4 genome
Cov.:
30

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 submitterclinical testingAmbry GeneticsMay 23, 2023The c.395C>T (p.A132V) alteration is located in exon 2 (coding exon 1) of the TRIM43 gene. This alteration results from a C to T substitution at nucleotide position 395, causing the alanine (A) at amino acid position 132 to be replaced by a valine (V). 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
0.17
BayesDel_addAF
Benign
-0.19
T
BayesDel_noAF
Benign
-0.51
CADD
Benign
16
DANN
Uncertain
1.0
DEOGEN2
Benign
0.16
T
Eigen
Benign
-0.46
Eigen_PC
Benign
-0.75
FATHMM_MKL
Benign
0.0065
N
LIST_S2
Benign
0.81
T
M_CAP
Benign
0.0049
T
MetaRNN
Benign
0.24
T
MetaSVM
Benign
-0.88
T
MutationAssessor
Uncertain
2.6
M
PrimateAI
Benign
0.39
T
PROVEAN
Uncertain
-2.7
D
REVEL
Benign
0.12
Sift
Uncertain
0.010
D
Sift4G
Benign
0.078
T
Polyphen
1.0
D
Vest4
0.11
MutPred
0.46
Gain of helix (P = 0.132);
MVP
0.67
MPC
0.53
ClinPred
0.79
D
GERP RS
-0.26
Varity_R
0.079
gMVP
0.13

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.26
Details are displayed if max score is > 0.2
DS_DG_spliceai
0.26
Position offset: -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: chr2-96260166; API