X-123614042-T-G

Variant names:

• chrX-123614042-T-G
• rs191054518
• NM_001081550.2:c.4449+10A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001081550.2(THOC2):​c.4449+10A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 22)
• Consequence: THOC2 NM_001081550.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.00
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THOC2	NM_001081550.2	c.4449+10A>C		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+10A>C		intron_variant	Intron 34 of 38	5	NM_001081550.2	ENSP00000245838.8
THOC2	ENST00000355725.8	c.4449+10A>C		intron_variant	Intron 34 of 38	5		ENSP00000347959.4
THOC2	ENST00000491737.5	c.4104+10A>C		intron_variant	Intron 30 of 33	5		ENSP00000419795.1
THOC2	ENST00000441692.5	c.831+10A>C		intron_variant	Intron 5 of 9	5		ENSP00000415211.1
THOC2	ENST00000448128.5	c.234+10A>C		intron_variant	Intron 4 of 8	5		ENSP00000397317.1
THOC2	ENST00000416618.5	c.216+10A>C		intron_variant	Intron 3 of 7	5		ENSP00000415244.1
THOC2	ENST00000432353.5	n.*691+10A>C		intron_variant	Intron 4 of 8	1		ENSP00000415947.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	3.3
DANN	Benign	0.15
PhyloP100		-2.0
PromoterAI		0.021	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: rs191054518; hg19: chrX-122747893;