3-185919448-A-C
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate
The NM_004593.3(TRA2B):āc.771T>Gā(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 (ā ).
Frequency
Genomes: not found (cov: 32)
Exomes š: 6.8e-7 ( 0 hom. )
Consequence
TRA2B
NM_004593.3 missense
NM_004593.3 missense
Scores
1
5
13
Clinical Significance
Conservation
PhyloP100: 5.62
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 Uncertain_significance. Variant got 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant in gene, where missense usually causes diseases (based on misZ statistic), TRA2B. . Gene score misZ 3.4968 (greater than the threshold 3.09). Trascript score misZ 4.2084 (greater than threshold 3.09). GenCC has associacion of gene with complex neurodevelopmental disorder.
BP4
Computational evidence support a benign effect (MetaRNN=0.22938856).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TRA2B | NM_004593.3 | c.771T>G | p.Asp257Glu | missense_variant | 7/9 | ENST00000453386.7 | NP_004584.1 | |
TRA2B | NM_001243879.2 | c.471T>G | p.Asp157Glu | missense_variant | 6/8 | NP_001230808.1 | ||
TRA2B | XM_047448717.1 | c.471T>G | p.Asp157Glu | missense_variant | 7/9 | XP_047304673.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TRA2B | ENST00000453386.7 | c.771T>G | p.Asp257Glu | missense_variant | 7/9 | 1 | NM_004593.3 | ENSP00000416959.2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461314Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1AN XY: 727000
GnomAD4 exome
AF:
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1
AN:
1461314
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Cov.:
30
AF XY:
AC XY:
1
AN XY:
727000
Gnomad4 AFR exome
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GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
Asia WGS
AF:
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 submitter | clinical testing | Ambry Genetics | Jul 27, 2022 | The 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Uncertain
D;D
Sift4G
Benign
T;T
Polyphen
P;.
Vest4
MutPred
Gain of helix (P = 0.0325);.;
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at