Genetic Variant TRIM43B:p.Glu241Asp (chr2-95480320-C-A) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_001164464.2(TRIM43B):c.723G>T(p.Glu241Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 7/11 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0051 ( 5 hom., cov: 29)

Exomes 𝑓: 0.0012 ( 21 hom. )

Failed GnomAD Quality Control

Consequence

TRIM43B
NM_001164464.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.65

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0042305887).

BP6

Variant 2-95480320-C-A is Benign according to our data. Variant chr2-95480320-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 2348065.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIM43B	NM_001164464.2 link	c.723G>T	p.Glu241Asp	missense_variant	Exon 4 of 7	ENST00000639673.3	NP_001157936.1	A6NCK2
TRIM43B	XM_011511669.2 link	c.753G>T	p.Glu251Asp	missense_variant	Exon 4 of 7		XP_011509971.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIM43B	ENST00000639673.3 link	c.723G>T	p.Glu241Asp	missense_variant	Exon 4 of 7	1	NM_001164464.2	ENSP00000492719.1		A6NCK2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

761

AN:

149302

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0137

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00351

Gnomad ASJ

AF:

0.000289

Gnomad EAS

AF:

0.000772

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00392

Gnomad MID

AF:

0.00637

Gnomad NFE

AF:

0.00171

Gnomad OTH

AF:

0.00195

GnomAD3 exomes

AF:

0.00114

AC:

279

AN:

245034

Hom.:

AF XY:

0.000906

AC XY:

120

AN XY:

132412

show subpopulations

Gnomad AFR exome

AF:

0.00971

Gnomad AMR exome

AF:

0.00111

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000388

Gnomad SAS exome

AF:

0.000101

Gnomad FIN exome

AF:

0.0000466

Gnomad NFE exome

AF:

0.000671

Gnomad OTH exome

AF:

0.00100

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00121

AC:

1767

AN:

1454868

Hom.:

Cov.:

AF XY:

0.00115

AC XY:

833

AN XY:

723418

show subpopulations

Gnomad4 AFR exome

AF:

0.0117

Gnomad4 AMR exome

AF:

0.00219

Gnomad4 ASJ exome

AF:

0.000998

Gnomad4 EAS exome

AF:

0.000839

Gnomad4 SAS exome

AF:

0.000399

Gnomad4 FIN exome

AF:

0.00402

Gnomad4 NFE exome

AF:

0.000764

Gnomad4 OTH exome

AF:

0.00210

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00511

AC:

763

AN:

149412

Hom.:

Cov.:

AF XY:

0.00497

AC XY:

363

AN XY:

73036

show subpopulations

Gnomad4 AFR

AF:

0.0137

Gnomad4 AMR

AF:

0.00358

Gnomad4 ASJ

AF:

0.000289

Gnomad4 EAS

AF:

0.000774

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00392

Gnomad4 NFE

AF:

0.00171

Gnomad4 OTH

AF:

0.00193

Alfa

AF:

0.00537

Hom.:

ExAC

AF:

0.0000412

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Nov 12, 2021

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_noAF

Benign

-0.73

CADD

Benign

1.1

DANN

Benign

0.80

DEOGEN2

Benign

0.0034

T;T

FATHMM_MKL

Benign

0.00032

LIST_S2

Benign

0.040

T;.

MetaRNN

Benign

0.0042

T;T

MutationAssessor

Benign

-3.0

N;N

PrimateAI

Uncertain

0.64

GERP RS

-0.0066

Varity_R

0.054

gMVP

0.023

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