16-3025998-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.20

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]

ACMG classification

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	HGVSp	Effect	#exon/exons	MANE	UniProt
THOC6	NM_024339.5	c.220+10C>G		intron_variant		ENST00000326266.13
THOC6	NM_001142350.3	c.220+10C>G		intron_variant
THOC6	NM_001347703.2	c.148+10C>G		intron_variant
THOC6	NM_001347704.2	c.220+10C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
THOC6	ENST00000326266.13	c.220+10C>G		intron_variant		1	NM_024339.5	P1

Frequencies

GnomAD3 genomes AF: 0.627 AC: 95253 AN: 151956 Hom.: 30516 Cov.: 32

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

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.: 63 AF XY: 0.590 AC XY: 428904 AN XY: 727220

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.: 32 AF XY: 0.623 AC XY: 46268 AN XY: 74324

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:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

THOC6-related developmental delay-microcephaly-facial dysmorphism syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 10, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 31, 2020

- -

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

Other links and lift over

dbSNP: rs2245000; hg19: chr16-3075999; COSMIC: COSV50187569; COSMIC: COSV50187569;