ENST00000432645.6:c.3030C>A

Variant names:

• chr7-18954247-C-A
• rs2389998
• ENST00000432645.6:c.3030C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000432645.6(HDAC9):​c.3030C>A​(p.Phe1010Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. F1010F) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HDAC9 ENST00000432645.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.337
• Publications: 17 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.054276526).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000432645.6. 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.3022+17C>A		intron	N/A	NP_848512.1	Q9UKV0-7
	HDAC9	NM_058176.2		c.3030C>A	p.Phe1010Leu	missense	Exon 23 of 23	NP_478056.1	Q9UKV0-1
	HDAC9	NM_178423.3		c.3013+17C>A		intron	N/A	NP_848510.1	Q9UKV0-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HDAC9	ENST00000432645.6	TSL:1	c.3030C>A	p.Phe1010Leu	missense	Exon 23 of 23	ENSP00000410337.2	Q9UKV0-1
	HDAC9	ENST00000686413.1	MANE Select	c.3022+17C>A		intron	N/A	ENSP00000509161.1	Q9UKV0-7
	HDAC9	ENST00000441542.7	TSL:1	c.3022+17C>A		intron	N/A	ENSP00000408617.2	Q9UKV0-7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1218886 Hom.: 0 Cov.: 18 AF XY: 0.00 AC XY: 0 AN XY: 609564

African (AFR) AF: 0.00 AC: 0 AN: 27720

American (AMR) AF: 0.00 AC: 0 AN: 34700

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23916

East Asian (EAS) AF: 0.00 AC: 0 AN: 35330

South Asian (SAS) AF: 0.00 AC: 0 AN: 73760

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49520

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5048

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 916898

Other (OTH) AF: 0.00 AC: 0 AN: 51994

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.34
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	1.8
DANN	Benign	0.55
DEOGEN2	Benign	0.34	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.070	N
LIST_S2	Benign	0.22	T
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.054	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.34
PROVEAN	Benign	-0.17	N
REVEL	Benign	0.047
Sift	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.14
MutPred		0.30		Gain of helix (P = 0.0425)
MVP		0.55
ClinPred		0.052	T
GERP RS		1.5
Varity_R		0.042
Mutation Taster		=100/0	polymorphism

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: rs2389998; hg19: chr7-18993870;