Variant chr22-29512036-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_003678.5(THOC5):c.1782C>T(p.Asn594=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00507 in 1,613,932 control chromosomes in the GnomAD database, including 275 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.022 ( 137 hom., cov: 33)

Exomes 𝑓: 0.0033 ( 138 hom. )

Consequence

THOC5
NM_003678.5 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.54

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 22-29512036-G-A is Benign according to our data. Variant chr22-29512036-G-A is described in ClinVar as [Benign]. Clinvar id is 790774.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-3.54 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0739 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.1782C>T	p.Asn594=	synonymous_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.1782C>T	p.Asn594=	synonymous_variant	18/20	1	NM_003678.5	P1

Frequencies

GnomAD3 genomes

AF:

0.0224

AC:

3406

AN:

152146

Hom.:

137

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0762

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00844

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00972

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.000470

Gnomad OTH

AF:

0.0163

GnomAD3 exomes

AF:

0.00728

AC:

1830

AN:

251420

Hom.:

AF XY:

0.00605

AC XY:

822

AN XY:

135888

show subpopulations

Gnomad AFR exome

AF:

0.0773

Gnomad AMR exome

AF:

0.00521

Gnomad ASJ exome

AF:

0.000298

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0101

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000431

Gnomad OTH exome

AF:

0.00538

GnomAD4 exome

AF:

0.00327

AC:

4776

AN:

1461668

Hom.:

138

Cov.:

AF XY:

0.00331

AC XY:

2410

AN XY:

727148

show subpopulations

Gnomad4 AFR exome

AF:

0.0803

Gnomad4 AMR exome

AF:

0.00584

Gnomad4 ASJ exome

AF:

0.000995

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0107

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000341

Gnomad4 OTH exome

AF:

0.00704

GnomAD4 genome

AF:

0.0224

AC:

3413

AN:

152264

Hom.:

137

Cov.:

AF XY:

0.0217

AC XY:

1616

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.0762

Gnomad4 AMR

AF:

0.00843

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00973

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000470

Gnomad4 OTH

AF:

0.0161

Alfa

AF:

0.00843

Hom.:

Bravo

AF:

0.0256

Asia WGS

AF:

0.0100

AC:

AN:

3478

EpiCase

AF:

0.00109

EpiControl

AF:

0.000652

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

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.51

DANN

Benign

0.81

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