Variant 22-29519039-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_003678.5(THOC5):c.1456C>T(p.Arg486Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000549 in 1,456,938 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

THOC5
NM_003678.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.70

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 Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.907

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
THOC5	NM_003678.5 linkuse as main transcript	c.1456C>T	p.Arg486Cys	missense_variant	15/20	ENST00000490103.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
THOC5	ENST00000490103.6 linkuse as main transcript	c.1456C>T	p.Arg486Cys	missense_variant	15/20	1	NM_003678.5	P1
	ENST00000411969.1 linkuse as main transcript	n.162-5023C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000807

AC:

AN:

247838

Hom.:

AF XY:

0.00

AC XY:

AN XY:

133890

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.0000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000549

AC:

AN:

1456938

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

724394

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000506

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.0000332

GnomAD4 genome

Cov.:

Alfa

AF:

0.000130

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000165

AC:

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 23, 2024

The c.1456C>T (p.R486C) alteration is located in exon 16 (coding exon 14) of the THOC5 gene. This alteration results from a C to T substitution at nucleotide position 1456, causing the arginine (R) at amino acid position 486 to be replaced by a cysteine (C). 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

Uncertain

0.55

BayesDel_addAF

Pathogenic

0.27

BayesDel_noAF

Pathogenic

0.14

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.62

D;D;D;D

Eigen

Pathogenic

0.92

Eigen_PC

Pathogenic

0.92

FATHMM_MKL

Pathogenic

0.99

M_CAP

Benign

0.034

MetaRNN

Pathogenic

0.91

D;D;D;D

MetaSVM

Benign

-0.86

MutationAssessor

Uncertain

2.5

M;M;M;M

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Pathogenic

0.79

PROVEAN

Pathogenic

-6.8

D;D;D;D

REVEL

Uncertain

0.64

Sift

Uncertain

0.0010

D;D;D;D

Sift4G

Uncertain

0.0020

D;D;D;D

Polyphen

1.0

D;D;D;D

Vest4

0.91

MutPred

0.75

Loss of MoRF binding (P = 0.01);Loss of MoRF binding (P = 0.01);Loss of MoRF binding (P = 0.01);Loss of MoRF binding (P = 0.01);

MVP

0.64

MPC

1.3

ClinPred

1.0

GERP RS

5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.85

gMVP

0.83

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