2-95480399-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001164464.2(TRIM43B):​c.644G>A​(p.Ser215Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000447 in 1,609,508 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 30)
Exomes 𝑓: 0.000026 ( 0 hom. )

Consequence

TRIM43B
NM_001164464.2 missense

Scores

1
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0320
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.037121594).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TRIM43BNM_001164464.2 linkc.644G>A p.Ser215Asn missense_variant Exon 4 of 7 ENST00000639673.3 NP_001157936.1 A6NCK2
TRIM43BXM_011511669.2 linkc.674G>A p.Ser225Asn missense_variant Exon 4 of 7 XP_011509971.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TRIM43BENST00000639673.3 linkc.644G>A p.Ser215Asn missense_variant Exon 4 of 7 1 NM_001164464.2 ENSP00000492719.1 A6NCK2

Frequencies

GnomAD3 genomes
AF:
0.000217
AC:
33
AN:
151764
Hom.:
0
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.000775
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.00
Gnomad OTH
AF:
0.000479
GnomAD3 exomes
AF:
0.0000443
AC:
8
AN:
180676
Hom.:
0
AF XY:
0.0000520
AC XY:
5
AN XY:
96160
show subpopulations
Gnomad AFR exome
AF:
0.000512
Gnomad AMR exome
AF:
0.000111
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000261
AC:
38
AN:
1457624
Hom.:
0
Cov.:
32
AF XY:
0.0000248
AC XY:
18
AN XY:
724924
show subpopulations
Gnomad4 AFR exome
AF:
0.000876
Gnomad4 AMR exome
AF:
0.0000674
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000234
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.0000332
GnomAD4 genome
AF:
0.000224
AC:
34
AN:
151884
Hom.:
0
Cov.:
30
AF XY:
0.000135
AC XY:
10
AN XY:
74238
show subpopulations
Gnomad4 AFR
AF:
0.000797
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.000474
Bravo
AF:
0.000234
ExAC
AF:
0.0000336
AC:
4

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Aug 12, 2021
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.644G>A (p.S215N) alteration is located in exon 4 (coding exon 3) of the TRIM43B gene. This alteration results from a G to A substitution at nucleotide position 644, causing the serine (S) at amino acid position 215 to be replaced by an asparagine (N). 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
0.15
BayesDel_noAF
Benign
-0.92
CADD
Benign
4.1
DANN
Benign
0.34
DEOGEN2
Benign
0.029
T;T
FATHMM_MKL
Benign
0.0024
N
LIST_S2
Benign
0.33
T;.
MetaRNN
Benign
0.037
T;T
MutationAssessor
Benign
1.5
L;L
PrimateAI
Uncertain
0.60
T
GERP RS
0.40
Varity_R
0.044
gMVP
0.057

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.

Other links and lift over

dbSNP: rs563777718; hg19: chr2-96146147; API