Variant 5-175968168-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_032361.4(THOC3):c.41G>A(p.Gly14Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000656 in 152,416 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000015 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

THOC3
NM_032361.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.812

Variant links:

Genes affected

THOC3 (HGNC:19072): (THO complex subunit 3) This gene encodes a component of the nuclear THO transcription elongation complex, which is part of the larger transcription export (TREX) complex that couples messenger RNA processing and export. In humans, the transcription export complex is recruited to the 5'-end of messenger RNAs in a splicing- and cap-dependent manner. Studies of a related complex in mouse suggest that the metazoan transcription export complex is involved in cell differentiation and development. A pseudogene of this gene has been defined on chromosome 5. [provided by RefSeq, May 2013]

THOC3 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.09792182).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
THOC3	NM_032361.4 linkuse as main transcript	c.41G>A	p.Gly14Asp	missense_variant	1/6	ENST00000265097.9	NP_115737.1	Q96J01-1
THOC3	NM_001376902.1 linkuse as main transcript	c.41G>A	p.Gly14Asp	missense_variant	1/5		NP_001363831.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
THOC3	ENST00000265097.9 linkuse as main transcript	c.41G>A	p.Gly14Asp	missense_variant	1/6	1	NM_032361.4	ENSP00000265097.5		Q96J01-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152298

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.000478

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000152

AC:

AN:

1448070

Hom.:

Cov.:

AF XY:

0.00000556

AC XY:

AN XY:

719484

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000507

Gnomad4 SAS exome

AF:

0.0000118

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

AF:

0.00000656

AC:

AN:

152416

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74536

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000473

ExAC

AF:

0.0000676

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 12, 2021

The c.41G>A (p.G14D) alteration is located in exon 1 (coding exon 1) of the THOC3 gene. This alteration results from a G to A substitution at nucleotide position 41, causing the glycine (G) at amino acid position 14 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

0.18

BayesDel_addAF

Benign

-0.051

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.012

T;.;.

Eigen

Benign

-0.023

Eigen_PC

Benign

-0.035

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.74

T;T;T

M_CAP

Uncertain

0.19

MetaRNN

Benign

0.098

T;T;T

MetaSVM

Benign

-0.51

MutationAssessor

Benign

0.34

N;.;N

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-0.55

N;.;N

REVEL

Benign

0.16

Sift

Uncertain

0.019

D;.;D

Sift4G

Benign

0.096

T;D;T

Polyphen

1.0

D;.;.

Vest4

0.43

MutPred

0.14

Loss of glycosylation at P10 (P = 0.187);Loss of glycosylation at P10 (P = 0.187);Loss of glycosylation at P10 (P = 0.187);

MVP

0.51

ClinPred

0.087

GERP RS

4.2

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.7

Varity_R

0.23

gMVP

0.46

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

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