Genetic Variant THOC2:c.4449+10A>T (chrX-123614042-T-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001081550.2(THOC2):c.4449+10A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000939 in 1,193,145 control chromosomes in the GnomAD database, including 1 homozygotes. There are 57 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.000045 ( 0 hom., 3 hem., cov: 22)

Exomes 𝑓: 0.000099 ( 1 hom. 54 hem. )

Consequence

THOC2
NM_001081550.2 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.00

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

X-linked intellectual disability-short stature-overweight syndrome
Inheritance: XL Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics

THOC2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BP6

Variant X-123614042-T-A is Benign according to our data. Variant chrX-123614042-T-A is described in ClinVar as [Benign]. Clinvar id is 739835.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 3 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THOC2	NM_001081550.2 link	c.4449+10A>T		intron_variant	Intron 34 of 38	ENST00000245838.13	NP_001075019.1	Q8NI27-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
THOC2	ENST00000245838.13 link	c.4449+10A>T	intron_variant	Intron 34 of 38	5	NM_001081550.2	ENSP00000245838.8	Q8NI27-1
THOC2	ENST00000355725.8 link	c.4449+10A>T	intron_variant	Intron 34 of 38	5		ENSP00000347959.4	Q8NI27-1
THOC2	ENST00000491737.5 link	c.4104+10A>T	intron_variant	Intron 30 of 33	5		ENSP00000419795.1	A0A0C4DG98
THOC2	ENST00000441692.5 link	c.831+10A>T	intron_variant	Intron 5 of 9	5		ENSP00000415211.1	H0Y7U4
THOC2	ENST00000448128.5 link	c.234+10A>T	intron_variant	Intron 4 of 8	5		ENSP00000397317.1	H0Y594
THOC2	ENST00000416618.5 link	c.216+10A>T	intron_variant	Intron 3 of 7	5		ENSP00000415244.1	B7ZBA0
THOC2	ENST00000432353.5 link	n.*691+10A>T	intron_variant	Intron 4 of 8	1		ENSP00000415947.1	H7C477

Frequencies

GnomAD3 genomes

AF:

0.0000450

AC:

AN:

111053

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000326

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000287

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000379

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000226

AC:

AN:

163549

AF XY:

0.000237

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000438

Gnomad ASJ exome

AF:

0.00

Gnomad EAS 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:

0.0000989

AC:

107

AN:

1082092

Hom.:

Cov.:

AF XY:

0.000153

AC XY:

AN XY:

353716

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25830

American (AMR)

AF:

0.000385

AC:

AN:

33749

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18819

East Asian (EAS)

AF:

0.00

AC:

AN:

30061

South Asian (SAS)

AF:

0.00176

AC:

AN:

52264

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34299

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4063

European-Non Finnish (NFE)

AF:

0.00000119

AC:

AN:

837435

Other (OTH)

AF:

0.0000219

AC:

AN:

45572

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000450

AC:

AN:

111053

Hom.:

Cov.:

AF XY:

0.0000899

AC XY:

AN XY:

33383

show subpopulations

African (AFR)

AF:

0.0000326

AC:

AN:

30710

American (AMR)

AF:

0.000287

AC:

AN:

10441

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2633

East Asian (EAS)

AF:

0.00

AC:

AN:

3553

South Asian (SAS)

AF:

0.000379

AC:

AN:

2638

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5989

Middle Eastern (MID)

AF:

0.00

AC:

AN:

239

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

52676

Other (OTH)

AF:

0.00

AC:

AN:

1493

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000727

Hom.:

Bravo

AF:

0.0000378

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Apr 10, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

3.1

(source)

DANN

Benign

0.13

PhyloP100

-2.0

PromoterAI

0.0044

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

X-123614042-T-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over