dbSNP rs34096894: HDAC9:p.Leu155Leu (chr7-18591563-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_178425.4(HDAC9):c.463C>T(p.Leu155Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0102 in 1,612,396 control chromosomes in the GnomAD database, including 801 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 0.043 ( 392 hom., cov: 32)

Exomes 𝑓: 0.0068 ( 409 hom. )

Consequence

HDAC9
NM_178425.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.02

Publications

4 publications found

Variant links:

Genes affected

HDAC9 (HGNC:14065): (histone deacetylase 9) 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 has sequence homology to members of the histone deacetylase family. This gene is orthologous to the Xenopus and mouse MITR genes. The MITR protein lacks the histone deacetylase catalytic domain. It represses MEF2 activity through recruitment of multicomponent corepressor complexes that include CtBP and HDACs. This encoded protein may play a role in hematopoiesis. Multiple alternatively spliced transcripts have been described for this gene but the full-length nature of some of them has not been determined. [provided by RefSeq, Jul 2008]

HDAC9 Gene-Disease associations (from GenCC):

auriculocondylar syndrome 4
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

HDAC9 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.34).

BP7

Synonymous conserved (PhyloP=1.02 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HDAC9	NM_178425.4 link	c.463C>T	p.Leu155Leu	synonymous_variant	Exon 5 of 26	ENST00000686413.1	NP_848512.1	Q9UKV0-7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HDAC9	ENST00000686413.1 link	c.463C>T	p.Leu155Leu	synonymous_variant	Exon 5 of 26		NM_178425.4	ENSP00000509161.1		Q9UKV0-7

Frequencies

GnomAD3 genomes

AF:

0.0425

AC:

6447

AN:

151574

Hom.:

384

Cov.:

show subpopulations

Gnomad AFR

AF:

0.139

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0230

Gnomad ASJ

AF:

0.0329

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.0000951

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.00272

Gnomad OTH

AF:

0.0347

GnomAD2 exomes

AF:

0.0143

AC:

3535

AN:

247492

AF XY:

0.0118

show subpopulations

Gnomad AFR exome

AF:

0.146

Gnomad AMR exome

AF:

0.0140

Gnomad ASJ exome

AF:

0.0370

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000186

Gnomad NFE exome

AF:

0.00299

Gnomad OTH exome

AF:

0.0133

GnomAD4 exome

AF:

0.00678

AC:

9906

AN:

1460704

Hom.:

409

Cov.:

AF XY:

0.00633

AC XY:

4602

AN XY:

726560

show subpopulations

African (AFR)

AF:

0.142

AC:

4752

AN:

33444

American (AMR)

AF:

0.0155

AC:

691

AN:

44500

Ashkenazi Jewish (ASJ)

AF:

0.0351

AC:

915

AN:

26098

East Asian (EAS)

AF:

0.00

AC:

AN:

39682

South Asian (SAS)

AF:

0.000953

AC:

AN:

86082

European-Finnish (FIN)

AF:

0.000300

AC:

AN:

53320

Middle Eastern (MID)

AF:

0.0274

AC:

158

AN:

5764

European-Non Finnish (NFE)

AF:

0.00218

AC:

2425

AN:

1111488

Other (OTH)

AF:

0.0144

AC:

867

AN:

60326

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

453

906

1360

1813

2266

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0426

AC:

6467

AN:

151692

Hom.:

392

Cov.:

AF XY:

0.0405

AC XY:

3000

AN XY:

74150

show subpopulations

African (AFR)

AF:

0.139

AC:

5727

AN:

41264

American (AMR)

AF:

0.0229

AC:

349

AN:

15214

Ashkenazi Jewish (ASJ)

AF:

0.0329

AC:

114

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5166

South Asian (SAS)

AF:

0.00104

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.0000951

AC:

AN:

10512

Middle Eastern (MID)

AF:

0.0476

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00272

AC:

185

AN:

67946

Other (OTH)

AF:

0.0343

AC:

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

275

551

826

1102

1377

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0225

Hom.:

131

Bravo

AF:

0.0488

Asia WGS

AF:

0.00636

AC:

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.34

CADD

Benign

7.3

(source)

DANN

Benign

0.73

PhyloP100

1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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.

rs34096894

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