Genetic Variant TRA2B:p.His98Arg (chr3-185925504-T-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_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. 14/23 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

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]

TRA2B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.056533843).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRA2B	NM_004593.3 link	c.293A>G	p.His98Arg	missense_variant	Exon 3 of 9	ENST00000453386.7	NP_004584.1	P62995-1
TRA2B	NM_001243879.2 link	c.-8A>G		5_prime_UTR_variant	Exon 2 of 8		NP_001230808.1	P62995-3
TRA2B	XM_047448717.1 link	c.-8A>G		5_prime_UTR_variant	Exon 3 of 9		XP_047304673.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRA2B	ENST00000453386.7 link	c.293A>G	p.His98Arg	missense_variant	Exon 3 of 9	1	NM_004593.3	ENSP00000416959.2		P62995-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000119

AC:

AN:

251328

AF XY:

0.00

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000103

AC:

AN:

1461840

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

727222

show subpopulations

Gnomad4 AFR exome

AF:

0.00

AC:

AN:

33478

Gnomad4 AMR exome

AF:

0.00

AC:

AN:

44722

Gnomad4 ASJ exome

AF:

0.00

AC:

AN:

26136

Gnomad4 EAS exome

AF:

0.0000252

AC:

AN:

39700

Gnomad4 SAS exome

AF:

0.00

AC:

AN:

86252

Gnomad4 FIN exome

AF:

0.00

AC:

AN:

53418

Gnomad4 NFE exome

AF:

0.0000117

AC:

AN:

1111980

Gnomad4 Remaining exome

AF:

0.0000166

AC:

AN:

60388

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000824

AC:

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

Dec 31, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The 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

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Benign

0.84

DEOGEN2

Benign

0.078

Eigen

Benign

-0.24

Eigen_PC

Benign

0.037

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.0048

MetaRNN

Benign

0.057

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.14

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-0.010

REVEL

Benign

0.069

Sift

Benign

0.68

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.20

MutPred

0.23

Loss of glycosylation at S99 (P = 0.0712);

MVP

0.12

MPC

1.7

ClinPred

0.15

GERP RS

6.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.19

gMVP

0.18

Mutation Taster

=236/64

polymorphism

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over