chrX-123614070-G-A

Variant names:

• chrX-123614070-G-A
• rs922460485
• NM_001081550.2:c.4431C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_001081550.2(THOC2):​c.4431C>T​(p.Asp1477Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000901 in 110,971 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. 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 0.0000090 (0 hom., 1 hem., cov: 22)
• Consequence: THOC2 NM_001081550.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.88
• 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 -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.172).
• BP7: Synonymous conserved (PhyloP=1.88 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THOC2	NM_001081550.2	c.4431C>T	p.Asp1477Asp	synonymous_variant	Exon 34 of 39	ENST00000245838.13	NP_001075019.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
THOC2	ENST00000245838.13	c.4431C>T	p.Asp1477Asp	synonymous_variant	Exon 34 of 39	5	NM_001081550.2	ENSP00000245838.8
THOC2	ENST00000355725.8	c.4431C>T	p.Asp1477Asp	synonymous_variant	Exon 34 of 39	5		ENSP00000347959.4
THOC2	ENST00000491737.5	c.4086C>T	p.Asp1362Asp	synonymous_variant	Exon 30 of 34	5		ENSP00000419795.1
THOC2	ENST00000441692.5	c.813C>T	p.Asp271Asp	synonymous_variant	Exon 5 of 10	5		ENSP00000415211.1
THOC2	ENST00000448128.5	c.216C>T	p.Asp72Asp	synonymous_variant	Exon 4 of 9	5		ENSP00000397317.1
THOC2	ENST00000416618.5	c.198C>T	p.Asp66Asp	synonymous_variant	Exon 3 of 8	5		ENSP00000415244.1
THOC2	ENST00000432353.5	n.*673C>T		non_coding_transcript_exon_variant	Exon 4 of 9	1		ENSP00000415947.1
THOC2	ENST00000432353.5	n.*673C>T		3_prime_UTR_variant	Exon 4 of 9	1		ENSP00000415947.1

Frequencies

GnomAD3 genomes AF: 0.00000901 AC: 1 AN: 110971 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000190

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 29

GnomAD4 genome AF: 0.00000901 AC: 1 AN: 110971 Hom.: 0 Cov.: 22 AF XY: 0.0000300 AC XY: 1 AN XY: 33357

African (AFR) AF: 0.00 AC: 0 AN: 30683

American (AMR) AF: 0.00 AC: 0 AN: 10441

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2628

East Asian (EAS) AF: 0.00 AC: 0 AN: 3547

South Asian (SAS) AF: 0.00 AC: 0 AN: 2653

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5940

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

European-Non Finnish (NFE) AF: 0.0000190 AC: 1 AN: 52655

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

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	9.3
DANN	Benign	0.50
PhyloP100		1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs922460485; hg19: chrX-122747921;