Genetic Variant THOC2:c.769-11dupT (chrX-123671771-T-TA) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_001081550.2(THOC2):c.769-11dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0045 in 1,006,010 control chromosomes in the GnomAD database, including 10 homozygotes. There are 290 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0016 ( 0 hom., 59 hem., cov: 23)

Exomes 𝑓: 0.0048 ( 10 hom. 231 hem. )

Consequence

THOC2
NM_001081550.2 intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.586

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 Benign. Variant got -16 ACMG points.

BP6

Variant X-123671771-T-TA is Benign according to our data. Variant chrX-123671771-T-TA is described in ClinVar as [Likely_benign]. Clinvar id is 445877.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00158 (170/107659) while in subpopulation SAS AF= 0.0205 (52/2541). AF 95% confidence interval is 0.016. There are 0 homozygotes in gnomad4. There are 59 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.

BS2

High Hemizygotes in GnomAd4 at 59 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THOC2	NM_001081550.2 link	c.769-11dupT		intron_variant	Intron 8 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.769-11_769-10insT	intron_variant	Intron 8 of 38	5	NM_001081550.2	ENSP00000245838.8	Q8NI27-1
THOC2	ENST00000355725.8 link	c.769-11_769-10insT	intron_variant	Intron 8 of 38	5		ENSP00000347959.4	Q8NI27-1
THOC2	ENST00000491737.5 link	c.424-11_424-10insT	intron_variant	Intron 4 of 33	5		ENSP00000419795.1	A0A0C4DG98
THOC2	ENST00000433883.1 link	n.399-11_399-10insT	intron_variant	Intron 8 of 9	5		ENSP00000415374.1	F2Z2V2

Frequencies

GnomAD3 genomes

AF:

0.00159

AC:

171

AN:

107628

Hom.:

Cov.:

AF XY:

0.00185

AC XY:

AN XY:

31370

show subpopulations

Gnomad AFR

AF:

0.000135

Gnomad AMI

AF:

0.00149

Gnomad AMR

AF:

0.00278

Gnomad ASJ

AF:

0.00659

Gnomad EAS

AF:

0.000288

Gnomad SAS

AF:

0.0212

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0212

Gnomad NFE

AF:

0.00111

Gnomad OTH

AF:

0.00279

GnomAD4 exome

AF:

0.00485

AC:

4355

AN:

898351

Hom.:

Cov.:

AF XY:

0.000893

AC XY:

231

AN XY:

258813

show subpopulations

Gnomad4 AFR exome

AF:

0.00379

Gnomad4 AMR exome

AF:

0.00646

Gnomad4 ASJ exome

AF:

0.00716

Gnomad4 EAS exome

AF:

0.00254

Gnomad4 SAS exome

AF:

0.0183

Gnomad4 FIN exome

AF:

0.00151

Gnomad4 NFE exome

AF:

0.00419

Gnomad4 OTH exome

AF:

0.00593

GnomAD4 genome

AF:

0.00158

AC:

170

AN:

107659

Hom.:

Cov.:

AF XY:

0.00188

AC XY:

AN XY:

31413

show subpopulations

Gnomad4 AFR

AF:

0.000134

Gnomad4 AMR

AF:

0.00277

Gnomad4 ASJ

AF:

0.00659

Gnomad4 EAS

AF:

0.000289

Gnomad4 SAS

AF:

0.0205

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00112

Gnomad4 OTH

AF:

0.00275

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

X-linked intellectual disability-short stature-overweight syndrome

Benign:1

Sep 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

May 08, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

X-123671771-TAAAAAA-TAAAAAAA

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