Variant 2-95481618-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000639673.3(TRIM43B):c.484A>G(p.Arg162Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000993 in 1,460,204 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 8/11 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00019 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000099 ( 2 hom. )

Failed GnomAD Quality Control

Consequence

TRIM43B
ENST00000639673.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.357

Variant links:

Genes affected

TRIM43B (HGNC:37146): (tripartite motif containing 43B) 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]

TRIM43B links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.026144654).

BS2

High Homozygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM43B	NM_001164464.2 linkuse as main transcript	c.484A>G	p.Arg162Gly	missense_variant	3/7	ENST00000639673.3	NP_001157936.1
TRIM43B	XM_011511669.2 linkuse as main transcript	c.514A>G	p.Arg172Gly	missense_variant	3/7		XP_011509971.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM43B	ENST00000639673.3 linkuse as main transcript	c.484A>G	p.Arg162Gly	missense_variant	3/7	1	NM_001164464.2	ENSP00000492719	P1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

151962

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.000411

Gnomad AMI

AF:

0.00220

Gnomad AMR

AF:

0.000263

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000736

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000129

AC:

AN:

248542

Hom.:

AF XY:

0.000134

AC XY:

AN XY:

134606

show subpopulations

Gnomad AFR exome

AF:

0.000445

Gnomad AMR exome

AF:

0.000349

Gnomad ASJ exome

AF:

0.0000998

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000132

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000534

Gnomad OTH exome

AF:

0.000331

GnomAD4 exome

AF:

0.0000993

AC:

145

AN:

1460204

Hom.:

Cov.:

AF XY:

0.000105

AC XY:

AN XY:

726286

show subpopulations

Gnomad4 AFR exome

AF:

0.000209

Gnomad4 AMR exome

AF:

0.000494

Gnomad4 ASJ exome

AF:

0.0000767

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000105

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.0000801

Gnomad4 OTH exome

AF:

0.000133

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000191

AC:

AN:

152078

Hom.:

Cov.:

AF XY:

0.000229

AC XY:

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.000410

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000736

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000432

Hom.:

ExAC

AF:

0.000115

AC:

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

Nov 08, 2021

The c.484A>G (p.R162G) alteration is located in exon 3 (coding exon 2) of the TRIM43B gene. This alteration results from a A to G substitution at nucleotide position 484, causing the arginine (R) at amino acid position 162 to be replaced by a glycine (G). 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

0.090

BayesDel_noAF

Benign

-0.97

CADD

Benign

2.0

DANN

Benign

0.49

DEOGEN2

Benign

0.015

T;T

FATHMM_MKL

Benign

0.0019

LIST_S2

Benign

0.20

T;.

MetaRNN

Benign

0.026

T;T

MutationAssessor

Benign

0.26

N;N

PrimateAI

Benign

0.46

GERP RS

-2.2

Varity_R

0.063

gMVP

0.064

Splicing

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