16-3025700-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_024339.5(THOC6):c.40-8C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.327 in 1,612,008 control chromosomes in the GnomAD database, including 88,565 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.30 (7217 hom., cov: 33)
  • Exomes 𝑓: 0.33 (81348 hom.)
• Consequence: THOC6 NM_024339.5 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.0001452
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.262

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 16-3025700-C-T is Benign according to our data. Variant chr16-3025700-C-T is described in ClinVar as [Benign]. Clinvar id is 1342292.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.341 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
THOC6	NM_024339.5	c.40-8C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000326266.13
THOC6	NM_001142350.3	c.40-8C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
THOC6	NM_001347703.2	c.-29-12C>T		splice_polypyrimidine_tract_variant, intron_variant
THOC6	NM_001347704.2	c.40-8C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
THOC6	ENST00000326266.13	c.40-8C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_024339.5	P1

Frequencies

GnomAD3 genomes AF: 0.301 AC: 45705 AN: 151958 Hom.: 7210 Cov.: 33

Gnomad AFR AF: 0.264

Gnomad AMI AF: 0.365

Gnomad AMR AF: 0.267

Gnomad ASJ AF: 0.365

Gnomad EAS AF: 0.178

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.272

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.345

Gnomad OTH AF: 0.302

GnomAD3 exomes AF: 0.290 AC: 72712 AN: 251030 Hom.: 11178 AF XY: 0.292 AC XY: 39610 AN XY: 135642

Gnomad AFR exome AF: 0.268

Gnomad AMR exome AF: 0.202

Gnomad ASJ exome AF: 0.349

Gnomad EAS exome AF: 0.178

Gnomad SAS exome AF: 0.241

Gnomad FIN exome AF: 0.283

Gnomad NFE exome AF: 0.346

Gnomad OTH exome AF: 0.301

GnomAD4 exome AF: 0.330 AC: 481088 AN: 1459932 Hom.: 81348 Cov.: 33 AF XY: 0.328 AC XY: 238256 AN XY: 726352

Gnomad4 AFR exome AF: 0.273

Gnomad4 AMR exome AF: 0.209

Gnomad4 ASJ exome AF: 0.349

Gnomad4 EAS exome AF: 0.193

Gnomad4 SAS exome AF: 0.249

Gnomad4 FIN exome AF: 0.286

Gnomad4 NFE exome AF: 0.350

Gnomad4 OTH exome AF: 0.314

GnomAD4 genome AF: 0.301 AC: 45731 AN: 152076 Hom.: 7217 Cov.: 33 AF XY: 0.294 AC XY: 21876 AN XY: 74338

Gnomad4 AFR AF: 0.264

Gnomad4 AMR AF: 0.267

Gnomad4 ASJ AF: 0.365

Gnomad4 EAS AF: 0.179

Gnomad4 SAS AF: 0.232

Gnomad4 FIN AF: 0.272

Gnomad4 NFE AF: 0.345

Gnomad4 OTH AF: 0.298

Alfa AF: 0.326 Hom.: 5736

Bravo AF: 0.295

Asia WGS AF: 0.189 AC: 660 AN: 3478

EpiCase AF: 0.349

EpiControl AF: 0.347

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	1.9
Dann	Benign	0.60
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00015
dbscSNV1_RF	Benign	0.018
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: rs2717664; hg19: chr16-3075701; COSMIC: COSV50187325; COSMIC: COSV50187325;