Menu
GeneBe

3-185919448-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate

The NM_004593.3(TRA2B):c.771T>G(p.Asp257Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,314 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

TRA2B
NM_004593.3 missense

Scores

1
5
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.62
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. 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=0.22938856).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TRA2BNM_004593.3 linkuse as main transcriptc.771T>G p.Asp257Glu missense_variant 7/9 ENST00000453386.7
TRA2BNM_001243879.2 linkuse as main transcriptc.471T>G p.Asp157Glu missense_variant 6/8
TRA2BXM_047448717.1 linkuse as main transcriptc.471T>G p.Asp157Glu missense_variant 7/9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TRA2BENST00000453386.7 linkuse as main transcriptc.771T>G p.Asp257Glu missense_variant 7/91 NM_004593.3 P2P62995-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461314
Hom.:
0
Cov.:
30
AF XY:
0.00000138
AC XY:
1
AN XY:
727000
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

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 GeneticsJul 27, 2022The c.771T>G (p.D257E) alteration is located in exon 7 (coding exon 7) of the TRA2B gene. This alteration results from a T to G substitution at nucleotide position 771, causing the aspartic acid (D) at amino acid position 257 to be replaced by a glutamic acid (E). 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
-0.067
T
BayesDel_noAF
Benign
-0.33
CADD
Uncertain
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.099
T;.
Eigen
Uncertain
0.28
Eigen_PC
Uncertain
0.41
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Benign
0.76
T;T
M_CAP
Benign
0.013
T
MetaRNN
Benign
0.23
T;T
MetaSVM
Benign
-0.90
T
MutationAssessor
Benign
1.1
L;.
MutationTaster
Benign
0.99
D;D
PrimateAI
Uncertain
0.75
T
PROVEAN
Benign
-0.60
N;N
REVEL
Benign
0.086
Sift
Uncertain
0.012
D;D
Sift4G
Benign
0.58
T;T
Polyphen
0.64
P;.
Vest4
0.49
MutPred
0.26
Gain of helix (P = 0.0325);.;
MVP
0.30
MPC
2.3
ClinPred
0.67
D
GERP RS
5.7
RBP_binding_hub_radar
1.1
RBP_regulation_power_radar
2.8
Varity_R
0.16
gMVP
0.80

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs1378378778; hg19: chr3-185637236; API