17-44087517-G-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005474.5(HDAC5):c.1779C>G(p.Asp593Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.746 in 1,610,846 control chromosomes in the GnomAD database, including 451,156 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.71 ( 38798 hom., cov: 31)

Exomes 𝑓: 0.75 ( 412358 hom. )

Consequence

HDAC5
NM_005474.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.837

Publications

47 publications found

Variant links:

Genes affected

HDAC5 (HGNC:14068): (histone deacetylase 5) Histones play a critical role in transcriptional regulation, cell cycle progression, and developmental events. Histone acetylation/deacetylation alters chromosome structure and affects transcription factor access to DNA. The protein encoded by this gene belongs to the class II histone deacetylase/acuc/apha family. It possesses histone deacetylase activity and represses transcription when tethered to a promoter. It coimmunoprecipitates only with HDAC3 family member and might form multicomplex proteins. It also interacts with myocyte enhancer factor-2 (MEF2) proteins, resulting in repression of MEF2-dependent genes. This gene is thought to be associated with colon cancer. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

HDAC5 Gene-Disease associations (from GenCC):

Tourette syndrome
Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

HDAC5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=8.665137E-7).

BP6

Variant 17-44087517-G-C is Benign according to our data. Variant chr17-44087517-G-C is described in ClinVar as Benign. ClinVar VariationId is 1300626.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.861 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HDAC5	NM_005474.5 link	c.1779C>G	p.Asp593Glu	missense_variant	Exon 13 of 27	ENST00000682912.1	NP_005465.2	Q9UQL6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HDAC5	ENST00000682912.1 link	c.1779C>G	p.Asp593Glu	missense_variant	Exon 13 of 27		NM_005474.5	ENSP00000507606.1		Q9UQL6-1

Frequencies

GnomAD3 genomes

AF:

0.709

AC:

107715

AN:

151858

Hom.:

38766

Cov.:

show subpopulations

Gnomad AFR

AF:

0.590

Gnomad AMI

AF:

0.717

Gnomad AMR

AF:

0.767

Gnomad ASJ

AF:

0.665

Gnomad EAS

AF:

0.832

Gnomad SAS

AF:

0.883

Gnomad FIN

AF:

0.785

Gnomad MID

AF:

0.712

Gnomad NFE

AF:

0.737

Gnomad OTH

AF:

0.724

GnomAD2 exomes

AF:

0.767

AC:

192349

AN:

250930

AF XY:

0.770

show subpopulations

Gnomad AFR exome

AF:

0.588

Gnomad AMR exome

AF:

0.840

Gnomad ASJ exome

AF:

0.663

Gnomad EAS exome

AF:

0.835

Gnomad FIN exome

AF:

0.776

Gnomad NFE exome

AF:

0.740

Gnomad OTH exome

AF:

0.754

GnomAD4 exome

AF:

0.750

AC:

1094459

AN:

1458872

Hom.:

412358

Cov.:

AF XY:

0.753

AC XY:

546780

AN XY:

725902

show subpopulations

African (AFR)

AF:

0.582

AC:

19444

AN:

33406

American (AMR)

AF:

0.834

AC:

37301

AN:

44700

Ashkenazi Jewish (ASJ)

AF:

0.661

AC:

17268

AN:

26108

East Asian (EAS)

AF:

0.838

AC:

33281

AN:

39694

South Asian (SAS)

AF:

0.861

AC:

74191

AN:

86206

European-Finnish (FIN)

AF:

0.778

AC:

41514

AN:

53386

Middle Eastern (MID)

AF:

0.724

AC:

4172

AN:

5760

European-Non Finnish (NFE)

AF:

0.742

AC:

822791

AN:

1109322

Other (OTH)

AF:

0.738

AC:

44497

AN:

60290

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

13025

26049

39074

52098

65123

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20170

40340

60510

80680

100850

<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:

0.709

AC:

107796

AN:

151974

Hom.:

38798

Cov.:

AF XY:

0.717

AC XY:

53263

AN XY:

74278

show subpopulations

African (AFR)

AF:

0.590

AC:

24438

AN:

41424

American (AMR)

AF:

0.767

AC:

11717

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.665

AC:

2307

AN:

3468

East Asian (EAS)

AF:

0.832

AC:

4287

AN:

5152

South Asian (SAS)

AF:

0.883

AC:

4253

AN:

4816

European-Finnish (FIN)

AF:

0.785

AC:

8308

AN:

10588

Middle Eastern (MID)

AF:

0.716

AC:

209

AN:

292

European-Non Finnish (NFE)

AF:

0.737

AC:

50097

AN:

67948

Other (OTH)

AF:

0.725

AC:

1526

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1552

3104

4655

6207

7759

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

838

1676

2514

3352

4190

<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:

0.728

Hom.:

27845

Bravo

AF:

0.699

TwinsUK

AF:

0.741

AC:

2746

ALSPAC

AF:

0.752

AC:

2897

ESP6500AA

AF:

0.583

AC:

2569

ESP6500EA

AF:

0.735

AC:

6317

ExAC

AF:

0.761

AC:

92408

Asia WGS

AF:

0.847

AC:

2940

AN:

3478

EpiCase

AF:

0.743

EpiControl

AF:

0.743

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Oct 13, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.058

BayesDel_addAF

Benign

-0.86

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.014

(source)

DANN

Benign

0.62

DEOGEN2

Benign

0.24

.;.;T

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.015

LIST_S2

Benign

0.056

T;T;T

MetaRNN

Benign

8.7e-7

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.48

.;N;N

PhyloP100

-0.84

PrimateAI

Uncertain

0.51

PROVEAN

Benign

0.070

N;N;.

REVEL

Benign

0.039

Sift

Benign

0.73

T;T;.

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.074

MutPred

0.22

.;Gain of solvent accessibility (P = 0.2601);Gain of solvent accessibility (P = 0.2601);

MPC

0.29

ClinPred

0.00077

GERP RS

1.4

Varity_R

0.033

gMVP

0.045

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over