rs2023938

Positions:

• chr7-18997152-T-C

Variant summary

Our verdict is Benign. Variant got -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

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HDAC9	NM_178425.4	c.*1090T>C		3_prime_UTR_variant	26/26	ENST00000686413.1	NP_848512.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HDAC9	ENST00000686413.1	c.*1090T>C		3_prime_UTR_variant	26/26		NM_178425.4	ENSP00000509161.1
HDAC9	ENST00000441542.7	c.*1090T>C		3_prime_UTR_variant	25/25	1		ENSP00000408617.2
HDAC9	ENST00000406451.8	c.*1090T>C		3_prime_UTR_variant	26/26	1		ENSP00000384657.3
HDAC9	ENST00000490851.5	n.2272T>C		non_coding_transcript_exon_variant	10/10	2

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

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

Gnomad4 AFR AF: 0.204

Gnomad4 AMR AF: 0.0887

Gnomad4 ASJ AF: 0.117

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.101

Gnomad4 FIN AF: 0.124

Gnomad4 NFE AF: 0.0974

Gnomad4 OTH AF: 0.113

Alfa AF: 0.101 Hom.: 1848

Bravo AF: 0.126

Asia WGS AF: 0.0470 AC: 165 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.5
DANN	Benign	0.54

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2023938; hg19: chr7-19036775;