rs34096894

Positions:

• chr7-18591563-C-T

Variant summary

Our verdict is Benign. Variant got -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

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
HDAC9	NM_178425.4	c.463C>T	p.Leu155Leu	synonymous_variant	5/26	ENST00000686413.1	NP_848512.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HDAC9	ENST00000686413.1	c.463C>T	p.Leu155Leu	synonymous_variant	5/26		NM_178425.4	ENSP00000509161.1

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

GnomAD3 exomes AF: 0.0143 AC: 3535 AN: 247492 Hom.: 166 AF XY: 0.0118 AC XY: 1587 AN XY: 134250

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 SAS exome AF: 0.000756

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

Gnomad4 AFR exome AF: 0.142

Gnomad4 AMR exome AF: 0.0155

Gnomad4 ASJ exome AF: 0.0351

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000953

Gnomad4 FIN exome AF: 0.000300

Gnomad4 NFE exome AF: 0.00218

Gnomad4 OTH exome AF: 0.0144

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

Gnomad4 AFR AF: 0.139

Gnomad4 AMR AF: 0.0229

Gnomad4 ASJ AF: 0.0329

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.0000951

Gnomad4 NFE AF: 0.00272

Gnomad4 OTH AF: 0.0343

Alfa AF: 0.0227 Hom.: 81

Bravo AF: 0.0488

Asia WGS AF: 0.00636 AC: 23 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
DANN	Benign	0.73

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

LitVar

Other links and lift over

dbSNP: rs34096894; hg19: chr7-18631186;