7-23505772-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_013293.5(TRA2A):​c.812G>A​(p.Arg271Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000577 in 1,561,030 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000057 ( 0 hom. )

Consequence

TRA2A
NM_013293.5 missense

Scores

6
4
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.29
Variant links:
Genes affected
TRA2A (HGNC:16645): (transformer 2 alpha homolog) This gene is a member of the transformer 2 homolog family and encodes a protein with several RRM (RNA recognition motif) domains. This phosphorylated nuclear protein binds to specific RNA sequences and plays a role in the regulation of pre-mRNA splicing. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2013]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TRA2ANM_013293.5 linkc.812G>A p.Arg271Gln missense_variant Exon 7 of 8 ENST00000297071.9 NP_037425.1 Q13595-1Q549U1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TRA2AENST00000297071.9 linkc.812G>A p.Arg271Gln missense_variant Exon 7 of 8 1 NM_013293.5 ENSP00000297071.4 Q13595-1

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
151912
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000941
AC:
2
AN:
212542
Hom.:
0
AF XY:
0.00000862
AC XY:
1
AN XY:
116046
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:
0.0000196
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000568
AC:
8
AN:
1409118
Hom.:
0
Cov.:
29
AF XY:
0.00000428
AC XY:
3
AN XY:
700708
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:
0.00000733
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000658
AC:
1
AN:
151912
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74200
show subpopulations
Gnomad4 AFR
AF:
0.00
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:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.00000610
Hom.:
0
Bravo
AF:
0.0000113
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000233
AC:
2
ExAC
AF:
0.0000247
AC:
3

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Oct 30, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.812G>A (p.R271Q) alteration is located in exon 7 (coding exon 7) of the TRA2A gene. This alteration results from a G to A substitution at nucleotide position 812, causing the arginine (R) at amino acid position 271 to be replaced by a glutamine (Q). 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
Pathogenic
0.80
BayesDel_addAF
Uncertain
0.083
D
BayesDel_noAF
Benign
-0.090
CADD
Uncertain
25
DANN
Uncertain
0.99
DEOGEN2
Benign
0.17
T;.;.;.
Eigen
Pathogenic
0.76
Eigen_PC
Pathogenic
0.75
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Benign
0.80
T;T;.;T
M_CAP
Benign
0.023
T
MetaRNN
Uncertain
0.55
D;D;D;D
MetaSVM
Benign
-0.82
T
MutationAssessor
Pathogenic
3.1
M;.;.;.
PrimateAI
Pathogenic
0.81
D
PROVEAN
Benign
-2.3
N;N;N;.
REVEL
Benign
0.20
Sift
Benign
0.33
T;T;T;.
Sift4G
Uncertain
0.056
T;D;T;T
Polyphen
0.98
D;.;.;.
Vest4
0.66
MVP
0.46
MPC
1.4
ClinPred
0.96
D
GERP RS
5.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.32
gMVP
0.61

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: rs141362754; hg19: chr7-23545391; API