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GeneBe

3-185918424-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP2

The NM_004593.3(TRA2B):c.797C>T(p.Ser266Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,888 control chromosomes in the GnomAD database, with no homozygous occurrence. 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

4
10
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.92
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 Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant where missense usually causes diseases, TRA2B

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TRA2BNM_004593.3 linkuse as main transcriptc.797C>T p.Ser266Phe missense_variant 8/9 ENST00000453386.7
TRA2BNM_001243879.2 linkuse as main transcriptc.497C>T p.Ser166Phe missense_variant 7/8
TRA2BXM_047448717.1 linkuse as main transcriptc.497C>T p.Ser166Phe missense_variant 8/9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TRA2BENST00000453386.7 linkuse as main transcriptc.797C>T p.Ser266Phe missense_variant 8/91 NM_004593.3 P2P62995-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1460888
Hom.:
0
Cov.:
29
AF XY:
0.00000138
AC XY:
1
AN XY:
726796
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.00e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

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

Submissions by phenotype

not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingGeneDxMar 31, 2023Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.99
BayesDel_addAF
Benign
-0.031
T
BayesDel_noAF
Benign
-0.28
CADD
Pathogenic
33
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.64
D;.
Eigen
Uncertain
0.52
Eigen_PC
Uncertain
0.50
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.91
D;D
M_CAP
Uncertain
0.15
D
MetaRNN
Uncertain
0.64
D;D
MetaSVM
Benign
-0.94
T
MutationAssessor
Uncertain
2.3
M;.
MutationTaster
Benign
1.0
D;D
PrimateAI
Pathogenic
0.87
D
PROVEAN
Uncertain
-4.3
D;D
REVEL
Benign
0.28
Sift
Uncertain
0.0010
D;D
Sift4G
Pathogenic
0.0010
D;D
Polyphen
0.98
D;.
Vest4
0.80
MutPred
0.34
Loss of phosphorylation at S266 (P = 0.0011);.;
MVP
0.29
MPC
1.8
ClinPred
0.99
D
GERP RS
4.4
Varity_R
0.56
gMVP
0.93

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.21
Details are displayed if max score is > 0.2
DS_AG_spliceai
0.21
Position offset: -13

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-185636212; API