X-123671771-TAAAAAA-T

Variant names:

• chrX-123671771-TAAAAAA-T
• rs201356571
• NM_001081550.2:c.769-16_769-11delTTTTTT

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001081550.2(THOC2):​c.769-16_769-11delTTTTTT variant causes a intron change. The variant allele was found at a frequency of 0.00000108 in 924,015 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: 0.0000011 (0 hom. 0 hem.)
• Consequence: THOC2 NM_001081550.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.24
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.769-16_769-11delTTTTTT		intron	N/A	NP_001075019.1
	THOC2	NM_001441235.1		c.769-16_769-11delTTTTTT		intron	N/A	NP_001428164.1
	THOC2	NM_001441236.1		c.769-16_769-11delTTTTTT		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.769-16_769-11delTTTTTT		intron	N/A	ENSP00000245838.8
	THOC2	ENST00000355725.8	TSL:5	c.769-16_769-11delTTTTTT		intron	N/A	ENSP00000347959.4
	THOC2	ENST00000491737.5	TSL:5	c.424-16_424-11delTTTTTT		intron	N/A	ENSP00000419795.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.00000108 AC: 1 AN: 924015 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 271363

African (AFR) AF: 0.00 AC: 0 AN: 21432

American (AMR) AF: 0.00 AC: 0 AN: 25414

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15629

East Asian (EAS) AF: 0.00 AC: 0 AN: 25894

South Asian (SAS) AF: 0.00 AC: 0 AN: 39605

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35968

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

European-Non Finnish (NFE) AF: 0.00000139 AC: 1 AN: 718099

Other (OTH) AF: 0.00 AC: 0 AN: 38621

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		6.2

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;