dbSNP rs2530223: HDAC3:p.Gln55Gln (chr5-141634927-T-C) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_003883.4(HDAC3):c.165A>G(p.Gln55Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.613 in 1,613,510 control chromosomes in the GnomAD database, including 308,611 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.67 ( 35290 hom., cov: 31)

Exomes 𝑓: 0.61 ( 273321 hom. )

Consequence

HDAC3
NM_003883.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.75

Publications

43 publications found

Variant links:

Genes affected

HDAC3 (HGNC:4854): (histone deacetylase 3) 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 histone deacetylase/acuc/apha family. It has histone deacetylase activity and represses transcription when tethered to a promoter. It may participate in the regulation of transcription through its binding with the zinc-finger transcription factor YY1. This protein can also down-regulate p53 function and thus modulate cell growth and apoptosis. This gene is regarded as a potential tumor suppressor gene. [provided by RefSeq, Jul 2008]

HDAC3 Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder
Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics
neurodevelopmental disorder
Inheritance: AD Classification: MODERATE Submitted by: G2P

HDAC3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BP7

Synonymous conserved (PhyloP=1.75 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.84 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HDAC3	NM_003883.4 link	c.165A>G	p.Gln55Gln	synonymous_variant	Exon 3 of 15	ENST00000305264.8	NP_003874.2	O15379-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HDAC3	ENST00000305264.8 link	c.165A>G	p.Gln55Gln	synonymous_variant	Exon 3 of 15	1	NM_003883.4	ENSP00000302967.3		O15379-1

Frequencies

GnomAD3 genomes

AF:

0.670

AC:

101711

AN:

151868

Hom.:

35233

Cov.:

show subpopulations

Gnomad AFR

AF:

0.847

Gnomad AMI

AF:

0.459

Gnomad AMR

AF:

0.694

Gnomad ASJ

AF:

0.570

Gnomad EAS

AF:

0.329

Gnomad SAS

AF:

0.641

Gnomad FIN

AF:

0.601

Gnomad MID

AF:

0.582

Gnomad NFE

AF:

0.604

Gnomad OTH

AF:

0.659

GnomAD2 exomes

AF:

0.623

AC:

156603

AN:

251384

AF XY:

0.617

show subpopulations

Gnomad AFR exome

AF:

0.854

Gnomad AMR exome

AF:

0.767

Gnomad ASJ exome

AF:

0.562

Gnomad EAS exome

AF:

0.303

Gnomad FIN exome

AF:

0.602

Gnomad NFE exome

AF:

0.599

Gnomad OTH exome

AF:

0.606

GnomAD4 exome

AF:

0.607

AC:

887792

AN:

1461524

Hom.:

273321

Cov.:

AF XY:

0.608

AC XY:

441945

AN XY:

727062

show subpopulations

African (AFR)

AF:

0.852

AC:

28530

AN:

33470

American (AMR)

AF:

0.763

AC:

34114

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.566

AC:

14774

AN:

26122

East Asian (EAS)

AF:

0.343

AC:

13632

AN:

39698

South Asian (SAS)

AF:

0.655

AC:

56445

AN:

86234

European-Finnish (FIN)

AF:

0.603

AC:

32206

AN:

53418

Middle Eastern (MID)

AF:

0.592

AC:

3358

AN:

5674

European-Non Finnish (NFE)

AF:

0.601

AC:

668192

AN:

1111822

Other (OTH)

AF:

0.605

AC:

36541

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

17861

35723

53584

71446

89307

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18240

36480

54720

72960

91200

<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:

0.670

AC:

101829

AN:

151986

Hom.:

35290

Cov.:

AF XY:

0.668

AC XY:

49614

AN XY:

74268

show subpopulations

African (AFR)

AF:

0.847

AC:

35137

AN:

41468

American (AMR)

AF:

0.694

AC:

10596

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.570

AC:

1978

AN:

3472

East Asian (EAS)

AF:

0.329

AC:

1697

AN:

5160

South Asian (SAS)

AF:

0.639

AC:

3070

AN:

4806

European-Finnish (FIN)

AF:

0.601

AC:

6346

AN:

10554

Middle Eastern (MID)

AF:

0.578

AC:

170

AN:

294

European-Non Finnish (NFE)

AF:

0.604

AC:

41028

AN:

67956

Other (OTH)

AF:

0.660

AC:

1388

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1593

3186

4779

6372

7965

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

796

1592

2388

3184

3980

<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:

0.629

Hom.:

94214

Bravo

AF:

0.681

Asia WGS

AF:

0.575

AC:

2001

AN:

3478

EpiCase

AF:

0.589

EpiControl

AF:

0.587

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

(source)

DANN

Benign

0.83

PhyloP100

1.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=91/9

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Computational scores

Splicing

Publications

Other links and lift over