X-123610951-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_001081550.2(THOC2):c.4767G>A(p.Ser1589=) 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

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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• 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 GnomAd at 4 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
THOC2	NM_001081550.2	c.4767G>A	p.Ser1589=	synonymous_variant	38/39	ENST00000245838.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
THOC2	ENST00000245838.13	c.4767G>A	p.Ser1589=	synonymous_variant	38/39	5	NM_001081550.2	P1

Frequencies

GnomAD3 genomes AF: 0.0000716 AC: 8 AN: 111672 Hom.: 0 Cov.: 22 AF XY: 0.000118 AC XY: 4 AN XY: 33904

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

GnomAD3 exomes AF: 0.0000904 AC: 16 AN: 177003 Hom.: 0 AF XY: 0.000143 AC XY: 9 AN XY: 63019

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 SAS 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

Gnomad4 AFR exome AF: 0.0000380

Gnomad4 AMR exome AF: 0.0000576

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000187

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000228

Gnomad4 OTH exome AF: 0.0000435

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

Gnomad4 AFR AF: 0.0000326

Gnomad4 AMR AF: 0.0000948

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000113

Gnomad4 OTH AF: 0.00

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

Benign, criteria provided, single submitter

clinical testing

Invitae

Aug 14, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
Cadd	Benign	7.6
Dann	Benign	0.71
RBP_binding_hub_radar		1.0
RBP_regulation_power_radar		2.7

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: rs369296561; hg19: chrX-122744802;