rs191054518

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chrX-123614042-T-A
• chrX-123614042-T-G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001081550.2(THOC2):​c.4449+10A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000939 in 1,193,145 control chromosomes in the GnomAD database, including 1 homozygotes. There are 57 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.000045 (0 hom., 3 hem., cov: 22)
  • Exomes 𝑓: 0.000099 (1 hom. 54 hem.)
• Consequence: THOC2 NM_001081550.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant X-123614042-T-A is Benign according to our data. Variant chrX-123614042-T-A is described in ClinVar as [Benign]. Clinvar id is 739835.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Hemizygotes in GnomAd4 at 3 XL gene

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.0000450 AC: 5 AN: 111053 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.0000326

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000287

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000379

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000226 AC: 37 AN: 163549 AF XY: 0.000237

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000438

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: 0.0000989 AC: 107 AN: 1082092 Hom.: 1 Cov.: 29 AF XY: 0.000153 AC XY: 54 AN XY: 353716

African (AFR) AF: 0.00 AC: 0 AN: 25830

American (AMR) AF: 0.000385 AC: 13 AN: 33749

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18819

East Asian (EAS) AF: 0.00 AC: 0 AN: 30061

South Asian (SAS) AF: 0.00176 AC: 92 AN: 52264

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34299

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4063

European-Non Finnish (NFE) AF: 0.00000119 AC: 1 AN: 837435

Other (OTH) AF: 0.0000219 AC: 1 AN: 45572

GnomAD4 genome AF: 0.0000450 AC: 5 AN: 111053 Hom.: 0 Cov.: 22 AF XY: 0.0000899 AC XY: 3 AN XY: 33383

African (AFR) AF: 0.0000326 AC: 1 AN: 30710

American (AMR) AF: 0.000287 AC: 3 AN: 10441

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2633

East Asian (EAS) AF: 0.00 AC: 0 AN: 3553

South Asian (SAS) AF: 0.000379 AC: 1 AN: 2638

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5989

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 239

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 52676

Other (OTH) AF: 0.00 AC: 0 AN: 1493

Alfa AF: 0.0000727 Hom.: 0

Bravo AF: 0.0000378

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Apr 10, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	3.1
DANN	Benign	0.13
PhyloP100		-2.0
PromoterAI		0.0044	Neutral
Mutation Taster		=100/0	polymorphism

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;