Variant chr22-29517289-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_003678.5(THOC5):c.1567G>A(p.Val523Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0059 in 1,614,190 control chromosomes in the GnomAD database, including 102 homozygotes. 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 Benign (★).

Frequency

Genomes: 𝑓 0.0076 ( 18 hom., cov: 33)

Exomes 𝑓: 0.0057 ( 84 hom. )

Consequence

THOC5
NM_003678.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.14

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:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003942013).

BP6

Variant 22-29517289-C-T is Benign according to our data. Variant chr22-29517289-C-T is described in ClinVar as [Benign]. Clinvar id is 782635.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 18 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
THOC5	NM_003678.5 linkuse as main transcript	c.1567G>A	p.Val523Met	missense_variant	16/20	ENST00000490103.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
THOC5	ENST00000490103.6 linkuse as main transcript	c.1567G>A	p.Val523Met	missense_variant	16/20	1	NM_003678.5	P1
	ENST00000411969.1 linkuse as main transcript	n.162-3273G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.00759

AC:

1156

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000555

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00144

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00269

Gnomad FIN

AF:

0.0524

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00780

Gnomad OTH

AF:

0.00334

GnomAD3 exomes

AF:

0.00848

AC:

2132

AN:

251388

Hom.:

AF XY:

0.00827

AC XY:

1124

AN XY:

135868

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.000926

Gnomad ASJ exome

AF:

0.000397

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00343

Gnomad FIN exome

AF:

0.0520

Gnomad NFE exome

AF:

0.00720

Gnomad OTH exome

AF:

0.00668

GnomAD4 exome

AF:

0.00572

AC:

8369

AN:

1461864

Hom.:

Cov.:

AF XY:

0.00594

AC XY:

4319

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.000538

Gnomad4 AMR exome

AF:

0.00101

Gnomad4 ASJ exome

AF:

0.000497

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00334

Gnomad4 FIN exome

AF:

0.0468

Gnomad4 NFE exome

AF:

0.00471

Gnomad4 OTH exome

AF:

0.00419

GnomAD4 genome

AF:

0.00760

AC:

1157

AN:

152326

Hom.:

Cov.:

AF XY:

0.00925

AC XY:

689

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.000553

Gnomad4 AMR

AF:

0.00144

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00290

Gnomad4 FIN

AF:

0.0524

Gnomad4 NFE

AF:

0.00781

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00645

Hom.:

Bravo

AF:

0.00314

TwinsUK

AF:

0.00378

AC:

ALSPAC

AF:

0.00285

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00686

AC:

ExAC

AF:

0.00787

AC:

955

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00414

EpiControl

AF:

0.00474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 19, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.048

T;T;T;T

Eigen

Benign

-0.068

Eigen_PC

Benign

0.0062

FATHMM_MKL

Benign

0.55

MetaRNN

Benign

0.0039

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

L;L;L;L

MutationTaster

Benign

0.98

D;D;D;D

PrimateAI

Benign

0.46

PROVEAN

Benign

0.020

N;N;N;N

REVEL

Benign

0.019

Sift

Benign

0.15

T;T;T;T

Sift4G

Benign

0.13

T;T;T;T

Polyphen

0.51

P;P;P;P

Vest4

0.095

MVP

0.23

MPC

0.38

ClinPred

0.0096

GERP RS

3.2

Varity_R

0.047

gMVP

0.32

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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