Variant 16-3025957-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000326266.13(THOC6):c.189G>C(p.Glu63Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

THOC6
ENST00000326266.13 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.203

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
THOC6	NM_024339.5 linkuse as main transcript	c.189G>C	p.Glu63Asp	missense_variant	3/13	ENST00000326266.13	NP_077315.2
THOC6	NM_001347704.2 linkuse as main transcript	c.189G>C	p.Glu63Asp	missense_variant	4/14		NP_001334633.1
THOC6	NM_001347703.2 linkuse as main transcript	c.117G>C	p.Glu39Asp	missense_variant	4/14		NP_001334632.1
THOC6	NM_001142350.3 linkuse as main transcript	c.189G>C	p.Glu63Asp	missense_variant	3/12		NP_001135822.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
THOC6	ENST00000326266.13 linkuse as main transcript	c.189G>C	p.Glu63Asp	missense_variant	3/13	1	NM_024339.5	ENSP00000326531	P1	Q86W42-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000795

AC:

AN:

251484

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135916

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461884

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 13, 2024

The c.189G>C (p.E63D) alteration is located in exon 3 (coding exon 3) of the THOC6 gene. This alteration results from a G to C substitution at nucleotide position 189, causing the glutamic acid (E) at amino acid position 63 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.040

T;.;.;.

Eigen

Benign

-0.41

Eigen_PC

Benign

-0.28

FATHMM_MKL

Benign

0.70

LIST_S2

Benign

0.80

T;.;T;T

M_CAP

Benign

0.0091

MetaRNN

Benign

0.11

T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.6

L;.;.;L

MutationTaster

Benign

0.93

D;D;D;D

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-1.0

N;.;.;N

REVEL

Benign

0.081

Sift4G

Benign

0.20

T;T;T;T

Polyphen

0.016

B;.;.;B

Vest4

0.28

MutPred

0.33

Loss of methylation at K66 (P = 0.0989);.;.;Loss of methylation at K66 (P = 0.0989);

MVP

0.54

MPC

0.087

ClinPred

0.043

GERP RS

1.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.43

gMVP

0.20

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.22

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.22

Position offset: 4

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