rs10236525

Variant names:

• chr7-18372049-T-C
• rs10236525
• NM_001321868.2:c.26-124213T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001321868.2(HDAC9):​c.26-124213T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 152,112 control chromosomes in the GnomAD database, including 3,586 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 0.21 (3586 hom., cov: 32)
• Consequence: HDAC9 NM_001321868.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0590
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.227 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HDAC9	NM_001321868.2	c.26-124213T>C		intron_variant	Intron 2 of 25		NP_001308797.1
HDAC9	NM_001321869.2	c.26-124213T>C		intron_variant	Intron 2 of 12		NP_001308798.1
HDAC9	NM_001321870.2	c.26-124213T>C		intron_variant	Intron 2 of 12		NP_001308799.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HDAC9	ENST00000417496.6	c.26-86793T>C		intron_variant	Intron 2 of 12	2		ENSP00000401669.2
HDAC9	ENST00000707077.1	c.26-124213T>C		intron_variant	Intron 2 of 11			ENSP00000516728.1
HDAC9	ENST00000413509.6	c.-42+81534T>C		intron_variant	Intron 1 of 3	5		ENSP00000412497.2

Frequencies

GnomAD3 genomes AF: 0.212 AC: 32220 AN: 151994 Hom.: 3586 Cov.: 32

Gnomad AFR AF: 0.178

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.233

Gnomad ASJ AF: 0.183

Gnomad EAS AF: 0.209

Gnomad SAS AF: 0.151

Gnomad FIN AF: 0.259

Gnomad MID AF: 0.119

Gnomad NFE AF: 0.228

Gnomad OTH AF: 0.205

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.212 AC: 32227 AN: 152112 Hom.: 3586 Cov.: 32 AF XY: 0.211 AC XY: 15683 AN XY: 74350

African (AFR) AF: 0.178 AC: 7387 AN: 41492

American (AMR) AF: 0.233 AC: 3564 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.183 AC: 636 AN: 3470

East Asian (EAS) AF: 0.209 AC: 1081 AN: 5180

South Asian (SAS) AF: 0.150 AC: 724 AN: 4820

European-Finnish (FIN) AF: 0.259 AC: 2738 AN: 10566

Middle Eastern (MID) AF: 0.121 AC: 35 AN: 290

European-Non Finnish (NFE) AF: 0.228 AC: 15472 AN: 67986

Other (OTH) AF: 0.204 AC: 432 AN: 2114

Alfa AF: 0.219 Hom.: 10686

Bravo AF: 0.208

Asia WGS AF: 0.231 AC: 801 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.0
DANN	Benign	0.54
PhyloP100		-0.059
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10236525; hg19: chr7-18411672;