NM_178425.4:c.1731+17133T>C

Variant names:

• chr7-18683609-T-C
• rs73313346
• NM_178425.4:c.1731+17133T>C

Variant summary

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

The NM_178425.4(HDAC9):​c.1731+17133T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.041 in 152,220 control chromosomes in the GnomAD database, including 256 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 0.041 (256 hom., cov: 33)
• Consequence: HDAC9 NM_178425.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.439
• Publications: 5 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

ENSG00000295734 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.108 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HDAC9	NM_178425.4	MANE Select	c.1731+17133T>C		intron	N/A	NP_848512.1
	HDAC9	NM_178423.3		c.1722+17133T>C		intron	N/A	NP_848510.1
	HDAC9	NM_001321868.2		c.1656+17133T>C		intron	N/A	NP_001308797.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HDAC9	ENST00000686413.1	MANE Select	c.1731+17133T>C		intron	N/A	ENSP00000509161.1
	HDAC9	ENST00000441542.7	TSL:1	c.1731+17133T>C		intron	N/A	ENSP00000408617.2
	HDAC9	ENST00000406451.8	TSL:1	c.1722+17133T>C		intron	N/A	ENSP00000384657.3

Frequencies

GnomAD3 genomes AF: 0.0409 AC: 6222 AN: 152102 Hom.: 256 Cov.: 33

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0182

Gnomad ASJ AF: 0.0308

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0207

Gnomad FIN AF: 0.0192

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0129

Gnomad OTH AF: 0.0306

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

GnomAD4 genome AF: 0.0410 AC: 6239 AN: 152220 Hom.: 256 Cov.: 33 AF XY: 0.0411 AC XY: 3058 AN XY: 74454

African (AFR) AF: 0.111 AC: 4594 AN: 41536

American (AMR) AF: 0.0181 AC: 276 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0308 AC: 107 AN: 3472

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5158

South Asian (SAS) AF: 0.0203 AC: 98 AN: 4830

European-Finnish (FIN) AF: 0.0192 AC: 204 AN: 10630

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0129 AC: 879 AN: 67996

Other (OTH) AF: 0.0302 AC: 64 AN: 2116

Alfa AF: 0.0259 Hom.: 47

Bravo AF: 0.0440

Asia WGS AF: 0.0160 AC: 57 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.67
DANN	Benign	0.70
PhyloP100		-0.44
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs73313346; hg19: chr7-18723232;