X-123656420-C-T

Position:

• chrX-123656420-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001081550.2(THOC2):​c.1386+9222G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.44 (9252 hom., 12597 hem., cov: 20)
• Consequence: THOC2 NM_001081550.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.921

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.717 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
THOC2	NM_001081550.2	c.1386+9222G>A		intron_variant		ENST00000245838.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
THOC2	ENST00000245838.13	c.1386+9222G>A		intron_variant		5	NM_001081550.2	P1
THOC2	ENST00000355725.8	c.1386+9222G>A		intron_variant		5		P1
THOC2	ENST00000491737.5	c.1041+9222G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.442 AC: 47309 AN: 107151 Hom.: 9241 Cov.: 20 AF XY: 0.422 AC XY: 12556 AN XY: 29777

Gnomad AFR AF: 0.725

Gnomad AMI AF: 0.288

Gnomad AMR AF: 0.403

Gnomad ASJ AF: 0.393

Gnomad EAS AF: 0.674

Gnomad SAS AF: 0.308

Gnomad FIN AF: 0.302

Gnomad MID AF: 0.518

Gnomad NFE AF: 0.300

Gnomad OTH AF: 0.441

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.442 AC: 47360 AN: 107188 Hom.: 9252 Cov.: 20 AF XY: 0.422 AC XY: 12597 AN XY: 29822

Gnomad4 AFR AF: 0.725

Gnomad4 AMR AF: 0.404

Gnomad4 ASJ AF: 0.393

Gnomad4 EAS AF: 0.674

Gnomad4 SAS AF: 0.309

Gnomad4 FIN AF: 0.302

Gnomad4 NFE AF: 0.300

Gnomad4 OTH AF: 0.445

Alfa AF: 0.279 Hom.: 2230

Bravo AF: 0.471

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.1
DANN	Benign	0.48

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: rs5958281; hg19: chrX-122790271;