Variant chr22-29512083-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003678.5(THOC5):c.1735G>A(p.Val579Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 1,613,602 control chromosomes in the GnomAD database, including 43,436 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.20 ( 3350 hom., cov: 32)

Exomes 𝑓: 0.23 ( 40086 hom. )

Consequence

THOC5
NM_003678.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.303

Variant links:

Genes affected

THOC5 (HGNC:19074): (THO complex subunit 5) Predicted to enable mRNA binding activity. Involved in several processes, including monocyte differentiation; negative regulation of DNA damage checkpoint; and viral mRNA export from host cell nucleus. Located in nucleoplasm. Part of THO complex part of transcription export complex. Colocalizes with chromosome, telomeric region. Implicated in breast carcinoma. [provided by Alliance of Genome Resources, Apr 2022]

THOC5 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.3370981E-4).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.416 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
THOC5	NM_003678.5 linkuse as main transcript	c.1735G>A	p.Val579Ile	missense_variant	18/20	ENST00000490103.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
THOC5	ENST00000490103.6 linkuse as main transcript	c.1735G>A	p.Val579Ile	missense_variant	18/20	1	NM_003678.5	P1

Frequencies

GnomAD3 genomes

AF:

0.199

AC:

30190

AN:

152032

Hom.:

3353

Cov.:

show subpopulations

Gnomad AFR

AF:

0.118

Gnomad AMI

AF:

0.190

Gnomad AMR

AF:

0.210

Gnomad ASJ

AF:

0.275

Gnomad EAS

AF:

0.431

Gnomad SAS

AF:

0.189

Gnomad FIN

AF:

0.188

Gnomad MID

AF:

0.241

Gnomad NFE

AF:

0.225

Gnomad OTH

AF:

0.225

GnomAD3 exomes

AF:

0.222

AC:

55746

AN:

251172

Hom.:

6791

AF XY:

0.223

AC XY:

30240

AN XY:

135748

show subpopulations

Gnomad AFR exome

AF:

0.115

Gnomad AMR exome

AF:

0.185

Gnomad ASJ exome

AF:

0.264

Gnomad EAS exome

AF:

0.433

Gnomad SAS exome

AF:

0.184

Gnomad FIN exome

AF:

0.198

Gnomad NFE exome

AF:

0.225

Gnomad OTH exome

AF:

0.232

GnomAD4 exome

AF:

0.228

AC:

333787

AN:

1461450

Hom.:

40086

Cov.:

AF XY:

0.227

AC XY:

165020

AN XY:

727004

show subpopulations

Gnomad4 AFR exome

AF:

0.123

Gnomad4 AMR exome

AF:

0.188

Gnomad4 ASJ exome

AF:

0.261

Gnomad4 EAS exome

AF:

0.466

Gnomad4 SAS exome

AF:

0.182

Gnomad4 FIN exome

AF:

0.197

Gnomad4 NFE exome

AF:

0.229

Gnomad4 OTH exome

AF:

0.233

GnomAD4 genome

AF:

0.198

AC:

30193

AN:

152152

Hom.:

3350

Cov.:

AF XY:

0.196

AC XY:

14615

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.118

Gnomad4 AMR

AF:

0.209

Gnomad4 ASJ

AF:

0.275

Gnomad4 EAS

AF:

0.431

Gnomad4 SAS

AF:

0.189

Gnomad4 FIN

AF:

0.188

Gnomad4 NFE

AF:

0.225

Gnomad4 OTH

AF:

0.223

Alfa

AF:

0.231

Hom.:

7687

Bravo

AF:

0.202

TwinsUK

AF:

0.214

AC:

795

ALSPAC

AF:

0.230

AC:

887

ESP6500AA

AF:

0.127

AC:

559

ESP6500EA

AF:

0.228

AC:

1957

ExAC

AF:

0.217

AC:

26378

Asia WGS

AF:

0.273

AC:

950

AN:

3478

EpiCase

AF:

0.237

EpiControl

AF:

0.236

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.058

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.71

CADD

Benign

1.0

DANN

Benign

0.73

DEOGEN2

Benign

0.028

T;T;T;T

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.017

LIST_S2

Benign

0.49

.;.;T;.

MetaRNN

Benign

0.00023

T;T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

-0.32

N;N;N;N

MutationTaster

Benign

1.0

P;P;P;P

PrimateAI

Benign

0.30

PROVEAN

Benign

0.40

N;N;N;N

REVEL

Benign

0.045

Sift

Benign

0.98

T;T;T;T

Sift4G

Benign

0.63

T;T;T;T

Polyphen

0.0

B;B;B;B

Vest4

0.022

MPC

0.31

ClinPred

0.00030

GERP RS

1.1

Varity_R

0.012

gMVP

0.11

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over