rs34096894

Variant names:

• chr7-18591563-C-T
• rs34096894
• NM_178425.4:c.463C>T
• HDAC9 p.Leu155Leu

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.02
• Publications: 4 publications found

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

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178425.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HDAC9	NM_178425.4	MANE Select	c.463C>T	p.Leu155Leu	synonymous	Exon 5 of 26	NP_848512.1	Q9UKV0-7
	HDAC9	NM_178423.3		c.454C>T	p.Leu152Leu	synonymous	Exon 5 of 26	NP_848510.1	Q9UKV0-5
	HDAC9	NM_001321868.2		c.520C>T	p.Leu174Leu	synonymous	Exon 6 of 26	NP_001308797.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HDAC9	ENST00000686413.1	MANE Select	c.463C>T	p.Leu155Leu	synonymous	Exon 5 of 26	ENSP00000509161.1	Q9UKV0-7
	HDAC9	ENST00000441542.7	TSL:1	c.463C>T	p.Leu155Leu	synonymous	Exon 4 of 25	ENSP00000408617.2	Q9UKV0-7
	HDAC9	ENST00000406451.8	TSL:1	c.454C>T	p.Leu152Leu	synonymous	Exon 5 of 26	ENSP00000384657.3	Q9UKV0-5

Frequencies

GnomAD3 genomes AF: 0.0425 AC: 6447 AN: 151574 Hom.: 384 Cov.: 32

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

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.: 34 AF XY: 0.00633 AC XY: 4602 AN XY: 726560

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: 0 AN: 39682

South Asian (SAS) AF: 0.000953 AC: 82 AN: 86082

European-Finnish (FIN) AF: 0.000300 AC: 16 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

GnomAD4 genome AF: 0.0426 AC: 6467 AN: 151692 Hom.: 392 Cov.: 32 AF XY: 0.0405 AC XY: 3000 AN XY: 74150

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: 0 AN: 5166

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4816

European-Finnish (FIN) AF: 0.0000951 AC: 1 AN: 10512

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.00272 AC: 185 AN: 67946

Other (OTH) AF: 0.0343 AC: 72 AN: 2098

Alfa AF: 0.0225 Hom.: 131

Bravo AF: 0.0488

Asia WGS AF: 0.00636 AC: 23 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	7.3
DANN	Benign	0.73
PhyloP100		1.0
Mutation Taster		=100/0	polymorphism (auto)

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

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

Other links and lift over

dbSNP: rs34096894;

hg19: chr7-18631186;