rs2389998

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr7-18954247-C-T
• chr7-18954247-C-A

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_058176.2(HDAC9):​c.3030C>T​(p.Phe1010Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.76 in 1,368,696 control chromosomes in the GnomAD database, including 395,978 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.77 (45700 hom., cov: 32)
  • Exomes 𝑓: 0.76 (350278 hom.)
• Consequence: HDAC9 NM_058176.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 7-18954247-C-T is Benign according to our data. Variant chr7-18954247-C-T is described in ClinVar as Benign. ClinVar VariationId is 402925.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.337 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.802 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_058176.2. 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>T		intron	N/A	NP_848512.1	Q9UKV0-7
	HDAC9	NM_058176.2		c.3030C>T	p.Phe1010Phe	synonymous	Exon 23 of 23	NP_478056.1	Q9UKV0-1
	HDAC9	NM_178423.3		c.3013+17C>T		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>T	p.Phe1010Phe	synonymous	Exon 23 of 23	ENSP00000410337.2	Q9UKV0-1
	HDAC9	ENST00000686413.1	MANE Select	c.3022+17C>T		intron	N/A	ENSP00000509161.1	Q9UKV0-7
	HDAC9	ENST00000441542.7	TSL:1	c.3022+17C>T		intron	N/A	ENSP00000408617.2	Q9UKV0-7

Frequencies

GnomAD3 genomes AF: 0.775 AC: 117682 AN: 151872 Hom.: 45654 Cov.: 32

Gnomad AFR AF: 0.809

Gnomad AMI AF: 0.702

Gnomad AMR AF: 0.809

Gnomad ASJ AF: 0.767

Gnomad EAS AF: 0.715

Gnomad SAS AF: 0.780

Gnomad FIN AF: 0.765

Gnomad MID AF: 0.759

Gnomad NFE AF: 0.754

Gnomad OTH AF: 0.762

GnomAD2 exomes AF: 0.776 AC: 122720 AN: 158116 AF XY: 0.774

Gnomad AFR exome AF: 0.805

Gnomad AMR exome AF: 0.872

Gnomad ASJ exome AF: 0.772

Gnomad EAS exome AF: 0.713

Gnomad FIN exome AF: 0.761

Gnomad NFE exome AF: 0.752

Gnomad OTH exome AF: 0.758

GnomAD4 exome AF: 0.758 AC: 921878 AN: 1216708 Hom.: 350278 Cov.: 18 AF XY: 0.759 AC XY: 461809 AN XY: 608528

African (AFR) AF: 0.802 AC: 22187 AN: 27674

American (AMR) AF: 0.862 AC: 29881 AN: 34662

Ashkenazi Jewish (ASJ) AF: 0.779 AC: 18614 AN: 23894

East Asian (EAS) AF: 0.704 AC: 24839 AN: 35302

South Asian (SAS) AF: 0.782 AC: 57631 AN: 73702

European-Finnish (FIN) AF: 0.759 AC: 37582 AN: 49508

Middle Eastern (MID) AF: 0.736 AC: 3709 AN: 5038

European-Non Finnish (NFE) AF: 0.752 AC: 687972 AN: 915012

Other (OTH) AF: 0.760 AC: 39463 AN: 51916

GnomAD4 genome AF: 0.775 AC: 117786 AN: 151988 Hom.: 45700 Cov.: 32 AF XY: 0.778 AC XY: 57762 AN XY: 74286

African (AFR) AF: 0.809 AC: 33565 AN: 41494

American (AMR) AF: 0.809 AC: 12323 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.767 AC: 2660 AN: 3470

East Asian (EAS) AF: 0.715 AC: 3685 AN: 5154

South Asian (SAS) AF: 0.779 AC: 3756 AN: 4822

European-Finnish (FIN) AF: 0.765 AC: 8084 AN: 10562

Middle Eastern (MID) AF: 0.759 AC: 223 AN: 294

European-Non Finnish (NFE) AF: 0.754 AC: 51239 AN: 67946

Other (OTH) AF: 0.765 AC: 1612 AN: 2108

Alfa AF: 0.764 Hom.: 28343

Bravo AF: 0.778

Asia WGS AF: 0.761 AC: 2636 AN: 3466

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.4
DANN	Benign	0.63
PhyloP100		0.34
Mutation Taster		=100/0	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: rs2389998; hg19: chr7-18993870; COSMIC: COSV67786182; COSMIC: COSV67786182;