X-123611491-A-G

Position:

chrX-123611491-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate

The NM_001081550.2(THOC2):c.4703T>C(p.Ile1568Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000169 in 1,185,201 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000090 ( 0 hom., 0 hem., cov: 22)

Exomes 𝑓: 9.3e-7 ( 0 hom. 0 hem. )

Consequence

THOC2
NM_001081550.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.68

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:

THOC2 (HGNC:):

THOC2 links:

Genome browser will be placed here

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), 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=0.090459764).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
THOC2	NM_001081550.2 linkuse as main transcript	c.4703T>C	p.Ile1568Thr	missense_variant	37/39	ENST00000245838.13	NP_001075019.1	Q8NI27-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
THOC2	ENST00000245838.13 linkuse as main transcript	c.4703T>C	p.Ile1568Thr	missense_variant	37/39	5	NM_001081550.2	ENSP00000245838.8	Q8NI27-1
THOC2	ENST00000355725.8 linkuse as main transcript	c.4703T>C	p.Ile1568Thr	missense_variant	37/39	5		ENSP00000347959.4	Q8NI27-1
THOC2	ENST00000491737.5 linkuse as main transcript	c.4358T>C	p.Ile1453Thr	missense_variant	33/34	5		ENSP00000419795.1	A0A0C4DG98
THOC2	ENST00000441692.5 linkuse as main transcript	c.1085T>C	p.Ile362Thr	missense_variant	8/10	5		ENSP00000415211.1	H0Y7U4
THOC2	ENST00000448128.5 linkuse as main transcript	c.488T>C	p.Ile163Thr	missense_variant	7/9	5		ENSP00000397317.1	H0Y594
THOC2	ENST00000416618.5 linkuse as main transcript	c.470T>C	p.Ile157Thr	missense_variant	6/8	5		ENSP00000415244.1	B7ZBA0
THOC2	ENST00000455053.5 linkuse as main transcript	c.182T>C	p.Ile61Thr	missense_variant	2/4	3		ENSP00000402168.1	B7ZB98
THOC2	ENST00000432353.5 linkuse as main transcript	n.*945T>C		non_coding_transcript_exon_variant	7/9	1		ENSP00000415947.1	H7C477
THOC2	ENST00000432353.5 linkuse as main transcript	n.*945T>C		3_prime_UTR_variant	7/9	1		ENSP00000415947.1	H7C477

Frequencies

GnomAD3 genomes

AF:

0.00000902

AC:

AN:

110917

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33149

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:

0.0000189

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000556

AC:

AN:

179726

Hom.:

AF XY:

0.00

AC XY:

AN XY:

65698

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:

0.0000123

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

9.31e-7

AC:

AN:

1074284

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

341910

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:

0.00000122

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000902

AC:

AN:

110917

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33149

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:

0.0000189

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ExAC

AF:

0.00000828

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

May 29, 2024

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

Benign

0.063

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.016

T;.;.;.;T;T

FATHMM_MKL

Benign

0.46

LIST_S2

Uncertain

0.86

D;T;T;T;.;D

M_CAP

Benign

0.0037

MetaRNN

Benign

0.090

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.20

N;.;.;.;N;.

PrimateAI

Uncertain

0.78

PROVEAN

Benign

0.17

N;.;D;N;N;N

REVEL

Benign

0.22

Sift

Benign

1.0

T;.;T;T;T;T

Sift4G

Benign

0.59

T;T;T;T;T;T

Polyphen

0.0

B;.;.;.;B;.

Vest4

0.13

MutPred

0.29

Gain of phosphorylation at I1568 (P = 0.0024);.;.;.;Gain of phosphorylation at I1568 (P = 0.0024);.;

MVP

0.13

MPC

0.99

ClinPred

0.16

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.11

gMVP

0.0047

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