5-175968153-C-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_032361.4(THOC3):​c.56G>T​(p.Gly19Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000105 in 152,306 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000012 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

THOC3
NM_032361.4 missense

Scores

1
2
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.58
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.059357733).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
THOC3NM_032361.4 linkc.56G>T p.Gly19Val missense_variant Exon 1 of 6 ENST00000265097.9 NP_115737.1 Q96J01-1
THOC3NM_001376902.1 linkc.56G>T p.Gly19Val missense_variant Exon 1 of 5 NP_001363831.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
THOC3ENST00000265097.9 linkc.56G>T p.Gly19Val missense_variant Exon 1 of 6 1 NM_032361.4 ENSP00000265097.5 Q96J01-1

Frequencies

GnomAD3 genomes
AF:
0.000105
AC:
16
AN:
152306
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000386
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:
0.00
GnomAD3 exomes
AF:
0.0000174
AC:
4
AN:
230482
Hom.:
0
AF XY:
0.00000788
AC XY:
1
AN XY:
126932
show subpopulations
Gnomad AFR exome
AF:
0.000320
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.0000117
AC:
17
AN:
1452940
Hom.:
0
Cov.:
33
AF XY:
0.00000969
AC XY:
7
AN XY:
722274
show subpopulations
Gnomad4 AFR exome
AF:
0.000421
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.0000167
GnomAD4 genome
AF:
0.000105
AC:
16
AN:
152306
Hom.:
0
Cov.:
32
AF XY:
0.000121
AC XY:
9
AN XY:
74414
show subpopulations
Gnomad4 AFR
AF:
0.000386
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:
0.00
Alfa
AF:
0.0000843
Hom.:
0
ExAC
AF:
0.0000251
AC:
3

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 25, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.56G>T (p.G19V) alteration is located in exon 1 (coding exon 1) of the THOC3 gene. This alteration results from a G to T substitution at nucleotide position 56, causing the glycine (G) at amino acid position 19 to be replaced by a valine (V). 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
0.092
BayesDel_addAF
Benign
-0.10
T
BayesDel_noAF
Benign
-0.38
CADD
Benign
19
DANN
Benign
0.94
DEOGEN2
Benign
0.011
T;.;.
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.21
N
LIST_S2
Benign
0.76
T;T;T
M_CAP
Benign
0.057
D
MetaRNN
Benign
0.059
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.55
N;.;N
PrimateAI
Pathogenic
0.80
T
PROVEAN
Benign
-1.3
N;.;N
REVEL
Benign
0.11
Sift
Uncertain
0.0080
D;.;D
Sift4G
Uncertain
0.020
D;D;D
Polyphen
0.099
B;.;.
Vest4
0.60
MVP
0.23
ClinPred
0.054
T
GERP RS
2.5
RBP_binding_hub_radar
0.92
RBP_regulation_power_radar
2.1
Varity_R
0.12
gMVP
0.33

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.

Other links and lift over

dbSNP: rs751169939; hg19: chr5-175395156; API