rs2046800831

Variant names:

• chrX-123614034-A-T
• rs2046800831
• NM_001081550.2:c.4449+18T>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001081550.2(THOC2):​c.4449+18T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,074,282 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0000090 (0 hom., 0 hem., cov: 22)
  • Exomes 𝑓: 0.0000019 (0 hom. 2 hem.)
  • Failed GnomAD Quality Control
• Consequence: THOC2 NM_001081550.2 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0190
• Publications: 0 publications found

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant X-123614034-A-T is Benign according to our data. Variant chrX-123614034-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 3768831.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Hemizygotes in GnomAdExome4 at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THOC2	NM_001081550.2	c.4449+18T>A		intron_variant	Intron 34 of 38	ENST00000245838.13	NP_001075019.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
THOC2	ENST00000245838.13	c.4449+18T>A		intron_variant	Intron 34 of 38	5	NM_001081550.2	ENSP00000245838.8
THOC2	ENST00000355725.8	c.4449+18T>A		intron_variant	Intron 34 of 38	5		ENSP00000347959.4
THOC2	ENST00000491737.5	c.4104+18T>A		intron_variant	Intron 30 of 33	5		ENSP00000419795.1
THOC2	ENST00000441692.5	c.831+18T>A		intron_variant	Intron 5 of 9	5		ENSP00000415211.1
THOC2	ENST00000448128.5	c.234+18T>A		intron_variant	Intron 4 of 8	5		ENSP00000397317.1
THOC2	ENST00000416618.5	c.216+18T>A		intron_variant	Intron 3 of 7	5		ENSP00000415244.1
THOC2	ENST00000432353.5	n.*691+18T>A		intron_variant	Intron 4 of 8	1		ENSP00000415947.1

Frequencies

GnomAD3 genomes AF: 0.00000900 AC: 1 AN: 111142 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000958

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000186 AC: 2 AN: 1074282 Hom.: 0 Cov.: 29 AF XY: 0.00000575 AC XY: 2 AN XY: 348006

African (AFR) AF: 0.00 AC: 0 AN: 25711

American (AMR) AF: 0.00 AC: 0 AN: 33562

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18614

East Asian (EAS) AF: 0.00 AC: 0 AN: 29986

South Asian (SAS) AF: 0.00 AC: 0 AN: 51319

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33337

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4037

European-Non Finnish (NFE) AF: 0.00000240 AC: 2 AN: 832421

Other (OTH) AF: 0.00 AC: 0 AN: 45295

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000900 AC: 1 AN: 111142 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 33474

African (AFR) AF: 0.00 AC: 0 AN: 30745

American (AMR) AF: 0.0000958 AC: 1 AN: 10436

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2627

East Asian (EAS) AF: 0.00 AC: 0 AN: 3562

South Asian (SAS) AF: 0.00 AC: 0 AN: 2627

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5998

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 237

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 52726

Other (OTH) AF: 0.00 AC: 0 AN: 1501

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Feb 25, 2025

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Likely 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	-0.87
CADD	Benign	0.91
DANN	Benign	0.39
PhyloP100		-0.019
PromoterAI		-0.0088	Neutral

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

Other links and lift over

dbSNP: rs2046800831; hg19: chrX-122747885;