rs181749437

chrX-123712831-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001081550.2(THOC2):c.130+19T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00136 in 1,067,915 control chromosomes in the GnomAD database, including 15 homozygotes. There are 370 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0068 (10 hom., 208 hem., cov: 23)
  • Exomes 𝑓: 0.00073 (5 hom. 162 hem.)
• Consequence: THOC2 NM_001081550.2 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.383

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant X-123712831-A-T is Benign according to our data. Variant chrX-123712831-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 445452.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00676 (758/112207) while in subpopulation AFR AF= 0.0226 (699/30947). AF 95% confidence interval is 0.0212. There are 10 homozygotes in gnomad4. There are 208 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 10 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
THOC2	NM_001081550.2	c.130+19T>A		intron_variant		ENST00000245838.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
THOC2	ENST00000245838.13	c.130+19T>A		intron_variant		5	NM_001081550.2	P1
THOC2	ENST00000355725.8	c.130+19T>A		intron_variant		5		P1
THOC2	ENST00000433883.1	c.130+19T>A		intron_variant, NMD_transcript_variant		5
THOC2	ENST00000419789.1	n.55+19T>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.00668 AC: 749 AN: 112154 Hom.: 10 Cov.: 23 AF XY: 0.00586 AC XY: 201 AN XY: 34322

Gnomad AFR AF: 0.0223

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00380

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: 0.0000939

Gnomad OTH AF: 0.00929

GnomAD3 exomes AF: 0.00229 AC: 310 AN: 135638 Hom.: 1 AF XY: 0.00140 AC XY: 57 AN XY: 40718

Gnomad AFR exome AF: 0.0266

Gnomad AMR exome AF: 0.000972

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000859

Gnomad FIN exome AF: 0.0000709

Gnomad NFE exome AF: 0.0000308

Gnomad OTH exome AF: 0.00130

GnomAD4 exome AF: 0.000728 AC: 696 AN: 955708 Hom.: 5 Cov.: 15 AF XY: 0.000587 AC XY: 162 AN XY: 275756

Gnomad4 AFR exome AF: 0.0258

Gnomad4 AMR exome AF: 0.00143

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000669

Gnomad4 FIN exome AF: 0.0000762

Gnomad4 NFE exome AF: 0.0000149

Gnomad4 OTH exome AF: 0.00159

GnomAD4 genome AF: 0.00676 AC: 758 AN: 112207 Hom.: 10 Cov.: 23 AF XY: 0.00605 AC XY: 208 AN XY: 34385

Gnomad4 AFR AF: 0.0226

Gnomad4 AMR AF: 0.00380

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000939

Gnomad4 OTH AF: 0.00917

Alfa AF: 0.00305 Hom.: 15

Bravo AF: 0.00820

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

May 08, 2017

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	8.5
Dann	Benign	0.77

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

Publications

LitVar

Other links and lift over

dbSNP: rs181749437; hg19: chrX-122846681;