2-95594418-C-T

Position:

• chr2-95594418-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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.124

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]

ACMG classification

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
TRIM43	NM_138800.3	c.395C>T	p.Ala132Val	missense_variant	2/7	ENST00000272395.3	NP_620155.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM43	ENST00000272395.3	c.395C>T	p.Ala132Val	missense_variant	2/7	1	NM_138800.3	ENSP00000272395.2

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

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 23, 2023

The 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;