Variant X-123610952-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4_ModerateBS2

The NM_001081550.2(THOC2):c.4766C>T(p.Ser1589Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000073 in 1,095,209 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. S1589S) has been classified as Benign.

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 0.0000073 ( 0 hom. 3 hem. )

Consequence

THOC2
NM_001081550.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.87

Variant links:

Genes affected

THOC2 (HGNC:19073): (THO complex subunit 2) The TREX multiprotein complex binds specifically to spliced mRNAs to facilitate mRNA export. The protein encoded by this gene is a member of the THO complex, a subset of the TREX complex. The encoded protein interacts with the THOC1 protein.[provided by RefSeq, Jun 2010]

THOC2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), THOC2. . Gene score misZ 5.5258 (greater than the threshold 3.09). GenCC has associacion of gene with X-linked intellectual disability-short stature-overweight syndrome.

BP4

Computational evidence support a benign effect (MetaRNN=0.25140375).

BS2

High Hemizygotes in GnomAdExome4 at 3 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
THOC2	NM_001081550.2 linkuse as main transcript	c.4766C>T	p.Ser1589Leu	missense_variant	38/39	ENST00000245838.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
THOC2	ENST00000245838.13 linkuse as main transcript	c.4766C>T	p.Ser1589Leu	missense_variant	38/39	5	NM_001081550.2	P1	Q8NI27-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000113

AC:

AN:

177144

Hom.:

AF XY:

0.0000158

AC XY:

AN XY:

63146

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000765

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000730

AC:

AN:

1095209

Hom.:

Cov.:

AF XY:

0.00000832

AC XY:

AN XY:

360713

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000576

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:

0.00000714

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

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 submitter

clinical testing

GeneDx

Apr 09, 2019

Has not been previously published as pathogenic or benign to our knowledge; In-silico analysis, which includes splice predictors and evolutionary conservation, is inconclusive as to whether the variant alters gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

-0.080

CADD

Pathogenic

DANN

Uncertain

0.98

DEOGEN2

Benign

0.033

T;.;.;.;T;T

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.88

D;D;T;T;.;D

M_CAP

Benign

0.0058

MetaRNN

Benign

0.25

T;T;T;T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.97

L;.;.;.;L;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-0.47

N;.;D;D;N;N

REVEL

Benign

0.20

Sift

Pathogenic

0.0

D;.;D;D;D;D

Sift4G

Pathogenic

0.0

D;T;D;T;D;D

Polyphen

0.90

P;.;.;.;P;.

Vest4

0.55

MutPred

0.22

Loss of phosphorylation at S1589 (P = 8e-04);.;.;.;Loss of phosphorylation at S1589 (P = 8e-04);.;

MVP

0.30

MPC

0.73

ClinPred

0.51

GERP RS

5.7

Varity_R

0.53

gMVP

0.033

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