chrX-123671771-TAA-T

Variant names:

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

Variant summary

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

The NM_001081550.2(THOC2):​c.769-12_769-11delTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000116 in 1,031,320 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000093 (0 hom., 0 hem., cov: 23)
  • Exomes 𝑓: 0.000012 (0 hom. 1 hem.)
• Consequence: THOC2 NM_001081550.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.485
• 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_769-11delTT		intron	N/A	NP_001075019.1
	THOC2	NM_001441235.1		c.769-12_769-11delTT		intron	N/A	NP_001428164.1
	THOC2	NM_001441236.1		c.769-12_769-11delTT		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.769-12_769-11delTT		intron	N/A	ENSP00000245838.8
	THOC2	ENST00000355725.8	TSL:5	c.769-12_769-11delTT		intron	N/A	ENSP00000347959.4
	THOC2	ENST00000491737.5	TSL:5	c.424-12_424-11delTT		intron	N/A	ENSP00000419795.1

Frequencies

GnomAD3 genomes AF: 0.00000929 AC: 1 AN: 107637 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000288

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

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

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000550

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000119 AC: 11 AN: 923683 Hom.: 0 AF XY: 0.00000369 AC XY: 1 AN XY: 271199

⚠️ 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: 21423

American (AMR) AF: 0.00 AC: 0 AN: 25408

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15627

East Asian (EAS) AF: 0.000232 AC: 6 AN: 25890

South Asian (SAS) AF: 0.0000253 AC: 1 AN: 39572

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35961

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3353

European-Non Finnish (NFE) AF: 0.00000418 AC: 3 AN: 717852

Other (OTH) AF: 0.0000259 AC: 1 AN: 38597

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00000328188), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00000929 AC: 1 AN: 107637 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 31377

African (AFR) AF: 0.00 AC: 0 AN: 29743

American (AMR) AF: 0.00 AC: 0 AN: 10090

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2578

East Asian (EAS) AF: 0.000288 AC: 1 AN: 3473

South Asian (SAS) AF: 0.00 AC: 0 AN: 2554

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5282

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 236

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 51577

Other (OTH) AF: 0.00 AC: 0 AN: 1435

Alfa AF: 0.00 Hom.: 1

Bravo AF: 0.0000151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.48

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs201356571; hg19: chrX-122805622; COSMIC: COSV55544978;