chrX-123671771-T-TAA

Variant names:

• chrX-123671771-T-TAA
• rs201356571
• NM_001081550.2:c.769-12_769-11dupTT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001081550.2(THOC2):​c.769-12_769-11dupTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000195 in 923,298 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.000019 (0 hom. 0 hem.)
• Consequence: THOC2 NM_001081550.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.586
• 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: Uncertain_significance. The variant received 0 ACMG points.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THOC2	NM_001081550.2	MANE Select	c.769-12_769-11dupTT		intron	N/A	NP_001075019.1
	THOC2	NM_001441235.1		c.769-12_769-11dupTT		intron	N/A	NP_001428164.1
	THOC2	NM_001441236.1		c.769-12_769-11dupTT		intron	N/A	NP_001428165.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THOC2	ENST00000245838.13	TSL:5 MANE Select	c.769-11_769-10insTT		intron	N/A	ENSP00000245838.8
	THOC2	ENST00000355725.8	TSL:5	c.769-11_769-10insTT		intron	N/A	ENSP00000347959.4
	THOC2	ENST00000491737.5	TSL:5	c.424-11_424-10insTT		intron	N/A	ENSP00000419795.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD2 exomes AF: 0.0000384 AC: 4 AN: 104086 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000823

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000195 AC: 18 AN: 923298 Hom.: 0 Cov.: 17 AF XY: 0.00 AC XY: 0 AN XY: 270976

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 21426

American (AMR) AF: 0.000118 AC: 3 AN: 25397

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15620

East Asian (EAS) AF: 0.0000386 AC: 1 AN: 25881

South Asian (SAS) AF: 0.000127 AC: 5 AN: 39477

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35950

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3351

European-Non Finnish (NFE) AF: 0.0000111 AC: 8 AN: 717608

Other (OTH) AF: 0.0000259 AC: 1 AN: 38588

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 23

Alfa AF: 0.00 Hom.: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.59

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs201356571; hg19: chrX-122805622;