X-123656420-C-T

Variant names:

• chrX-123656420-C-T
• rs5958281
• NM_001081550.2:c.1386+9222G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001081550.2(THOC2):​c.1386+9222G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.44 (9252 hom., 12597 hem., cov: 20)
• Consequence: THOC2 NM_001081550.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.921
• Publications: 1 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.717 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001081550.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THOC2	NM_001081550.2	MANE Select	c.1386+9222G>A		intron	N/A	NP_001075019.1
	THOC2	NM_001441235.1		c.1386+9222G>A		intron	N/A	NP_001428164.1
	THOC2	NM_001441236.1		c.1386+9222G>A		intron	N/A	NP_001428165.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THOC2	ENST00000245838.13	TSL:5 MANE Select	c.1386+9222G>A		intron	N/A	ENSP00000245838.8
	THOC2	ENST00000355725.8	TSL:5	c.1386+9222G>A		intron	N/A	ENSP00000347959.4
	THOC2	ENST00000491737.5	TSL:5	c.1041+9222G>A		intron	N/A	ENSP00000419795.1

Frequencies

GnomAD3 genomes AF: 0.442 AC: 47309 AN: 107151 Hom.: 9241 Cov.: 20

Gnomad AFR AF: 0.725

Gnomad AMI AF: 0.288

Gnomad AMR AF: 0.403

Gnomad ASJ AF: 0.393

Gnomad EAS AF: 0.674

Gnomad SAS AF: 0.308

Gnomad FIN AF: 0.302

Gnomad MID AF: 0.518

Gnomad NFE AF: 0.300

Gnomad OTH AF: 0.441

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.442 AC: 47360 AN: 107188 Hom.: 9252 Cov.: 20 AF XY: 0.422 AC XY: 12597 AN XY: 29822

African (AFR) AF: 0.725 AC: 21151 AN: 29166

American (AMR) AF: 0.404 AC: 4059 AN: 10054

Ashkenazi Jewish (ASJ) AF: 0.393 AC: 1025 AN: 2611

East Asian (EAS) AF: 0.674 AC: 2274 AN: 3375

South Asian (SAS) AF: 0.309 AC: 746 AN: 2416

European-Finnish (FIN) AF: 0.302 AC: 1583 AN: 5236

Middle Eastern (MID) AF: 0.530 AC: 105 AN: 198

European-Non Finnish (NFE) AF: 0.300 AC: 15582 AN: 52022

Other (OTH) AF: 0.445 AC: 646 AN: 1453

Alfa AF: 0.279 Hom.: 2230

Bravo AF: 0.471

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.1
DANN	Benign	0.48
PhyloP100		-0.92
Mutation Taster		=100/0	polymorphism (auto)

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: rs5958281; hg19: chrX-122790271;