X-123610951-C-T

Variant names:

• chrX-123610951-C-T
• rs369296561
• NM_001081550.2:c.4767G>A

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_001081550.2(THOC2):​c.4767G>A​(p.Ser1589Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000171 in 1,207,028 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 75 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.000072 (0 hom., 4 hem., cov: 22)
  • Exomes 𝑓: 0.00018 (0 hom. 71 hem.)
• Consequence: THOC2 NM_001081550.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.26
• Publications: 2 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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.043).
• BP6: Variant X-123610951-C-T is Benign according to our data. Variant chrX-123610951-C-T is described in ClinVar as [Benign]. Clinvar id is 764241.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.26 with no splicing effect.
• BS2: High Hemizygotes in GnomAd4 at 4 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THOC2	NM_001081550.2	c.4767G>A	p.Ser1589Ser	synonymous_variant	Exon 38 of 39	ENST00000245838.13	NP_001075019.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
THOC2	ENST00000245838.13	c.4767G>A	p.Ser1589Ser	synonymous_variant	Exon 38 of 39	5	NM_001081550.2	ENSP00000245838.8
THOC2	ENST00000355725.8	c.4767G>A	p.Ser1589Ser	synonymous_variant	Exon 38 of 39	5		ENSP00000347959.4
THOC2	ENST00000491737.5	c.4422G>A	p.Ser1474Ser	synonymous_variant	Exon 34 of 34	5		ENSP00000419795.1
THOC2	ENST00000441692.5	c.1149G>A	p.Ser383Ser	synonymous_variant	Exon 9 of 10	5		ENSP00000415211.1
THOC2	ENST00000448128.5	c.552G>A	p.Ser184Ser	synonymous_variant	Exon 8 of 9	5		ENSP00000397317.1
THOC2	ENST00000416618.5	c.528G>A	p.Ser176Ser	synonymous_variant	Exon 7 of 8	5		ENSP00000415244.1
THOC2	ENST00000455053.5	c.240G>A	p.Ser80Ser	synonymous_variant	Exon 3 of 4	3		ENSP00000402168.1
THOC2	ENST00000432353.5	n.*1009G>A		non_coding_transcript_exon_variant	Exon 8 of 9	1		ENSP00000415947.1
THOC2	ENST00000432353.5	n.*1009G>A		3_prime_UTR_variant	Exon 8 of 9	1		ENSP00000415947.1

Frequencies

GnomAD3 genomes AF: 0.0000716 AC: 8 AN: 111672 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.0000326

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000948

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: 0.000113

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000904 AC: 16 AN: 177003 AF XY: 0.000143

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000115

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000149

Gnomad OTH exome AF: 0.000230

GnomAD4 exome AF: 0.000181 AC: 198 AN: 1095356 Hom.: 0 Cov.: 28 AF XY: 0.000197 AC XY: 71 AN XY: 360888

African (AFR) AF: 0.0000380 AC: 1 AN: 26287

American (AMR) AF: 0.0000576 AC: 2 AN: 34730

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19329

East Asian (EAS) AF: 0.00 AC: 0 AN: 30040

South Asian (SAS) AF: 0.0000187 AC: 1 AN: 53571

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40498

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4129

European-Non Finnish (NFE) AF: 0.000228 AC: 192 AN: 840774

Other (OTH) AF: 0.0000435 AC: 2 AN: 45998

GnomAD4 genome AF: 0.0000716 AC: 8 AN: 111672 Hom.: 0 Cov.: 22 AF XY: 0.000118 AC XY: 4 AN XY: 33904

African (AFR) AF: 0.0000326 AC: 1 AN: 30682

American (AMR) AF: 0.0000948 AC: 1 AN: 10544

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2647

East Asian (EAS) AF: 0.00 AC: 0 AN: 3558

South Asian (SAS) AF: 0.00 AC: 0 AN: 2684

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5997

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 238

European-Non Finnish (NFE) AF: 0.000113 AC: 6 AN: 53139

Other (OTH) AF: 0.00 AC: 0 AN: 1502

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.000106

EpiCase AF: 0.000220

EpiControl AF: 0.000179

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 14, 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	-0.32
CADD	Benign	7.6
DANN	Benign	0.71
PhyloP100		1.3
RBP_binding_hub_radar		1.0
RBP_regulation_power_radar		2.7
Mutation Taster		=95/5	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: rs369296561; hg19: chrX-122744802;