Genetic Variant THOC6:c.220+10C>G (chr16-3025998-C-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_024339.5(THOC6):c.220+10C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.595 in 1,613,914 control chromosomes in the GnomAD database, including 288,820 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.63 ( 30578 hom., cov: 32)

Exomes 𝑓: 0.59 ( 258242 hom. )

Consequence

THOC6
NM_024339.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.20

Variant links:

Genes affected

THOC6 (HGNC:28369): (THO complex subunit 6) This gene encodes a subunit of the multi-protein THO complex, which is involved in coordination between transcription and mRNA processing. The THO complex is a component of the TREX (transcription/export) complex, which is involved in transcription and export of mRNAs. A missense mutation in this gene is associated with a neurodevelopmental disorder called Beaulieu-Boycott-Innes syndrome. [provided by RefSeq, Dec 2016]

THOC6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 16-3025998-C-G is Benign according to our data. Variant chr16-3025998-C-G is described in ClinVar as [Benign]. Clinvar id is 1276705.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.735 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
THOC6	NM_024339.5 link	c.220+10C>G	intron_variant	Intron 3 of 12	ENST00000326266.13	NP_077315.2	Q86W42-1
THOC6	NM_001347704.2 link	c.220+10C>G	intron_variant	Intron 4 of 13		NP_001334633.1	Q86W42-1
THOC6	NM_001347703.2 link	c.148+10C>G	intron_variant	Intron 4 of 13		NP_001334632.1	Q86W42-2
THOC6	NM_001142350.3 link	c.220+10C>G	intron_variant	Intron 3 of 11		NP_001135822.1	Q86W42-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
THOC6	ENST00000326266.13 link	c.220+10C>G		intron_variant	Intron 3 of 12	1	NM_024339.5	ENSP00000326531.8		Q86W42-1

Frequencies

GnomAD3 genomes

AF:

0.627

AC:

95253

AN:

151956

Hom.:

30516

Cov.:

show subpopulations

Gnomad AFR

AF:

0.742

Gnomad AMI

AF:

0.644

Gnomad AMR

AF:

0.612

Gnomad ASJ

AF:

0.578

Gnomad EAS

AF:

0.297

Gnomad SAS

AF:

0.525

Gnomad FIN

AF:

0.590

Gnomad MID

AF:

0.560

Gnomad NFE

AF:

0.602

Gnomad OTH

AF:

0.601

GnomAD3 exomes

AF:

0.582

AC:

146461

AN:

251466

Hom.:

43914

AF XY:

0.577

AC XY:

78392

AN XY:

135912

show subpopulations

Gnomad AFR exome

AF:

0.751

Gnomad AMR exome

AF:

0.654

Gnomad ASJ exome

AF:

0.564

Gnomad EAS exome

AF:

0.293

Gnomad SAS exome

AF:

0.541

Gnomad FIN exome

AF:

0.588

Gnomad NFE exome

AF:

0.596

Gnomad OTH exome

AF:

0.573

GnomAD4 exome

AF:

0.591

AC:

864362

AN:

1461840

Hom.:

258242

Cov.:

AF XY:

0.590

AC XY:

428904

AN XY:

727220

show subpopulations

Gnomad4 AFR exome

AF:

0.755

Gnomad4 AMR exome

AF:

0.647

Gnomad4 ASJ exome

AF:

0.565

Gnomad4 EAS exome

AF:

0.316

Gnomad4 SAS exome

AF:

0.550

Gnomad4 FIN exome

AF:

0.589

Gnomad4 NFE exome

AF:

0.599

Gnomad4 OTH exome

AF:

0.575

GnomAD4 genome

AF:

0.627

AC:

95372

AN:

152074

Hom.:

30578

Cov.:

AF XY:

0.623

AC XY:

46268

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.742

Gnomad4 AMR

AF:

0.612

Gnomad4 ASJ

AF:

0.578

Gnomad4 EAS

AF:

0.297

Gnomad4 SAS

AF:

0.527

Gnomad4 FIN

AF:

0.590

Gnomad4 NFE

AF:

0.602

Gnomad4 OTH

AF:

0.597

Alfa

AF:

0.616

Hom.:

5378

Bravo

AF:

0.633

Asia WGS

AF:

0.413

AC:

1439

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jan 31, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

THOC6-related developmental delay-microcephaly-facial dysmorphism syndrome

Benign:1

Sep 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

7.0

DANN

Benign

0.40

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over