Variant 3-63838470-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_025075.4(THOC7):c.167C>T(p.Thr56Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000217 in 1,609,426 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000022 ( 0 hom. )

Consequence

THOC7
NM_025075.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.79

Variant links:

Genes affected

THOC7 (HGNC:29874): (THO complex subunit 7) Predicted to enable RNA binding activity. Involved in mRNA export from nucleus and viral mRNA export from host cell nucleus. Located in cytosol and nuclear speck. Part of THO complex part of transcription export complex. Colocalizes with chromosome, telomeric region. [provided by Alliance of Genome Resources, Apr 2022]

THOC7 links:

C3orf49 (HGNC:25190): (chromosome 3 open reading frame 49)

C3orf49 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.30615944).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
THOC7	NM_025075.4 linkuse as main transcript	c.167C>T	p.Thr56Met	missense_variant	3/8	ENST00000295899.10
C3orf49	NM_001355236.2 linkuse as main transcript	c.850-6553G>A		intron_variant		ENST00000295896.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
THOC7	ENST00000295899.10 linkuse as main transcript	c.167C>T	p.Thr56Met	missense_variant	3/8	1	NM_025075.4	P1
C3orf49	ENST00000295896.13 linkuse as main transcript	c.850-6553G>A		intron_variant		2	NM_001355236.2	A2

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

151982

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000809

AC:

AN:

247112

Hom.:

AF XY:

0.0000149

AC XY:

AN XY:

133944

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000302

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:

0.00000890

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000220

AC:

AN:

1457444

Hom.:

Cov.:

AF XY:

0.0000248

AC XY:

AN XY:

725124

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000230

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000235

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000252

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000197

AC:

AN:

151982

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74224

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:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000597

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

Mar 22, 2023

The c.167C>T (p.T56M) alteration is located in exon 3 (coding exon 3) of the THOC7 gene. This alteration results from a C to T substitution at nucleotide position 167, causing the threonine (T) at amino acid position 56 to be replaced by a methionine (M). 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

0.10

BayesDel_addAF

Benign

-0.041

BayesDel_noAF

Benign

-0.21

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.027

T;T;.

Eigen

Benign

0.15

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.97

D;D;D

M_CAP

Benign

0.0065

MetaRNN

Benign

0.31

T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.20

N;.;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-0.14

N;.;.

REVEL

Benign

0.14

Sift

Benign

0.20

T;.;.

Sift4G

Benign

0.40

T;T;D

Polyphen

0.39

B;.;.

Vest4

0.51

MutPred

0.44

Gain of phosphorylation at S55 (P = 0.1562);.;.;

MVP

0.082

MPC

0.55

ClinPred

0.47

GERP RS

6.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.073

gMVP

0.50

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