Variant 5-175968091-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_032361.4(THOC3):c.118G>A(p.Glu40Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000617 in 1,458,726 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

THOC3
NM_032361.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.58

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]

THOC3 links:

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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	UniProt
THOC3	NM_032361.4 linkuse as main transcript	c.118G>A	p.Glu40Lys	missense_variant	1/6	ENST00000265097.9	NP_115737.1
THOC3	NM_001376902.1 linkuse as main transcript	c.118G>A	p.Glu40Lys	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.118G>A	p.Glu40Lys	missense_variant	1/6	1	NM_032361.4	ENSP00000265097	P1	Q96J01-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000617

AC:

AN:

1458726

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725616

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000810

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Jan 24, 2024

The c.118G>A (p.E40K) 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 118, causing the glutamic acid (E) at amino acid position 40 to be replaced by a lysine (K). 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

0.29

BayesDel_addAF

Uncertain

0.074

BayesDel_noAF

Benign

-0.13

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.013

T;.;.

Eigen

Benign

-0.18

Eigen_PC

Benign

0.016

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.80

T;T;T

M_CAP

Benign

0.017

MetaRNN

Uncertain

0.58

D;D;D

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

N;.;N

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-0.45

N;.;N

REVEL

Benign

0.18

Sift

Benign

0.37

T;.;T

Sift4G

Benign

0.80

T;T;T

Polyphen

0.0030

B;.;.

Vest4

0.75

MutPred

0.55

Gain of MoRF binding (P = 0.0055);Gain of MoRF binding (P = 0.0055);Gain of MoRF binding (P = 0.0055);

MVP

0.49

ClinPred

0.95

GERP RS

4.3

Varity_R

0.47

gMVP

0.60

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over