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GeneBe

3-185925504-T-C

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PM2PP2BP4_Strong

The NM_004593.3(TRA2B):c.293A>G(p.His98Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000103 in 1,461,840 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

TRA2B
NM_004593.3 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.02
Variant links:
Genes affected
TRA2B (HGNC:10781): (transformer 2 beta homolog) This gene encodes a nuclear protein which functions as sequence-specific serine/arginine splicing factor which plays a role in mRNA processing, splicing patterns, and gene expression. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2011]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant where missense usually causes diseases, TRA2B
BP4
Computational evidence support a benign effect (MetaRNN=0.056533843).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TRA2BNM_004593.3 linkuse as main transcriptc.293A>G p.His98Arg missense_variant 3/9 ENST00000453386.7
TRA2BNM_001243879.2 linkuse as main transcriptc.-8A>G 5_prime_UTR_variant 2/8
TRA2BXM_047448717.1 linkuse as main transcriptc.-8A>G 5_prime_UTR_variant 3/9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TRA2BENST00000453386.7 linkuse as main transcriptc.293A>G p.His98Arg missense_variant 3/91 NM_004593.3 P2P62995-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000119
AC:
3
AN:
251328
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135824
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
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:
0.0000264
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000103
AC:
15
AN:
1461840
Hom.:
0
Cov.:
30
AF XY:
0.00000963
AC XY:
7
AN XY:
727222
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000117
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000756
ExAC
AF:
0.00000824
AC:
1
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

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

Submissions by phenotype

Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsDec 31, 2023The c.293A>G (p.H98R) alteration is located in exon 3 (coding exon 3) of the TRA2B gene. This alteration results from a A to G substitution at nucleotide position 293, causing the histidine (H) at amino acid position 98 to be replaced by an arginine (R). 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
0.16
BayesDel_addAF
Benign
-0.36
T
BayesDel_noAF
Benign
-0.58
CADD
Benign
22
DANN
Benign
0.84
DEOGEN2
Benign
0.078
T
Eigen
Benign
-0.24
Eigen_PC
Benign
0.037
FATHMM_MKL
Uncertain
0.89
D
LIST_S2
Uncertain
0.94
D
M_CAP
Benign
0.0048
T
MetaRNN
Benign
0.057
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
-0.14
N
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.67
T
PROVEAN
Benign
-0.010
N
REVEL
Benign
0.069
Sift
Benign
0.68
T
Sift4G
Benign
1.0
T
Polyphen
0.0
B
Vest4
0.20
MutPred
0.23
Loss of glycosylation at S99 (P = 0.0712);
MVP
0.12
MPC
1.7
ClinPred
0.15
T
GERP RS
6.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.6
Varity_R
0.19
gMVP
0.18

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

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: rs772894949; hg19: chr3-185643292; API