dbSNP rs188617925: THOC5:p.Glu339Gln (chr22-29528129-C-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_003678.5(THOC5):c.1015G>C(p.Glu339Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000161 in 1,614,180 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

THOC5
NM_003678.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.97

Publications

1 publications found

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:

ENSG00000234208 (HGNC:):

ENSG00000234208 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_003678.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003678.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
THOC5	NM_003678.5	MANE Select	c.1015G>C	p.Glu339Gln	missense	Exon 11 of 20	NP_003669.4
THOC5	NM_001002877.2		c.1015G>C	p.Glu339Gln	missense	Exon 12 of 21	NP_001002877.1	Q13769
THOC5	NM_001002878.1		c.1015G>C	p.Glu339Gln	missense	Exon 12 of 21	NP_001002878.1	Q13769

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
THOC5	ENST00000490103.6	TSL:1 MANE Select	c.1015G>C	p.Glu339Gln	missense	Exon 11 of 20	ENSP00000420306.1	Q13769
THOC5	ENST00000853420.1		c.1165G>C	p.Glu389Gln	missense	Exon 12 of 21	ENSP00000523479.1
THOC5	ENST00000928658.1		c.1069G>C	p.Glu357Gln	missense	Exon 13 of 22	ENSP00000598717.1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152170

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

GnomAD2 exomes

AF:

0.0000199

AC:

AN:

251452

AF XY:

0.0000147

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000440

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000157

AC:

AN:

1461892

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

727246

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000198

AC:

AN:

1112010

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152288

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74468

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41560

American (AMR)

AF:

0.00

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68026

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.56

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.32

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.063

Eigen

Uncertain

0.41

Eigen_PC

Uncertain

0.48

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.013

MetaRNN

Uncertain

0.48

MetaSVM

Benign

-0.55

MutationAssessor

Uncertain

2.4

PhyloP100

7.0

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-0.78

REVEL

Benign

0.15

Sift

Benign

0.048

Sift4G

Benign

0.12

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.35

gMVP

0.44

Mutation Taster

=68/32

polymorphism

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over