NM_178425.4:c.*1090T>C

Variant names:

• chr7-18997152-T-C
• rs2023938
• NM_178425.4:c.*1090T>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.*1090T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 152,224 control chromosomes in the GnomAD database, including 1,388 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 0.13 (1388 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: HDAC9 NM_178425.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.01
• Publications: 68 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.201 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HDAC9	NM_178425.4	MANE Select	c.*1090T>C		3_prime_UTR	Exon 26 of 26	NP_848512.1	Q9UKV0-7
	HDAC9	NM_178423.3		c.*1090T>C		3_prime_UTR	Exon 26 of 26	NP_848510.1	Q9UKV0-5
	HDAC9	NM_001321868.2		c.*1090T>C		3_prime_UTR	Exon 26 of 26	NP_001308797.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HDAC9	ENST00000686413.1	MANE Select	c.*1090T>C		3_prime_UTR	Exon 26 of 26	ENSP00000509161.1	Q9UKV0-7
	HDAC9	ENST00000441542.7	TSL:1	c.*1090T>C		3_prime_UTR	Exon 25 of 25	ENSP00000408617.2	Q9UKV0-7
	HDAC9	ENST00000406451.8	TSL:1	c.*1090T>C		3_prime_UTR	Exon 26 of 26	ENSP00000384657.3	Q9UKV0-5

Frequencies

GnomAD3 genomes AF: 0.125 AC: 19041 AN: 152106 Hom.: 1387 Cov.: 32

Gnomad AFR AF: 0.205

Gnomad AMI AF: 0.0932

Gnomad AMR AF: 0.0890

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.0974

Gnomad OTH AF: 0.115

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.125 AC: 19046 AN: 152224 Hom.: 1388 Cov.: 32 AF XY: 0.124 AC XY: 9223 AN XY: 74442

African (AFR) AF: 0.204 AC: 8487 AN: 41524

American (AMR) AF: 0.0887 AC: 1355 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 406 AN: 3470

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5186

South Asian (SAS) AF: 0.101 AC: 488 AN: 4832

European-Finnish (FIN) AF: 0.124 AC: 1314 AN: 10588

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.0974 AC: 6625 AN: 68020

Other (OTH) AF: 0.113 AC: 239 AN: 2114

Alfa AF: 0.104 Hom.: 4063

Bravo AF: 0.126

Asia WGS AF: 0.0470 AC: 165 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.5
DANN	Benign	0.54
PhyloP100		2.0
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: rs2023938; hg19: chr7-19036775;