5-141624764-A-G

Position:

• chr5-141624764-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003883.4(HDAC3):​c.1217+444T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 154,658 control chromosomes in the GnomAD database, including 1,766 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 0.15 (1716 hom., cov: 31)
  • Exomes 𝑓: 0.18 (50 hom.)
• Consequence: HDAC3 NM_003883.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0860

Genes affected

HDAC3 (HGNC:4854): (histone deacetylase 3) 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 belongs to the histone deacetylase/acuc/apha family. It has histone deacetylase activity and represses transcription when tethered to a promoter. It may participate in the regulation of transcription through its binding with the zinc-finger transcription factor YY1. This protein can also down-regulate p53 function and thus modulate cell growth and apoptosis. This gene is regarded as a potential tumor suppressor gene. [provided by RefSeq, Jul 2008]

HDAC3 (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 (SAS) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HDAC3	NM_003883.4	c.1217+444T>C		intron_variant		ENST00000305264.8	NP_003874.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HDAC3	ENST00000305264.8	c.1217+444T>C		intron_variant		1	NM_003883.4	ENSP00000302967.3

Frequencies

GnomAD3 genomes AF: 0.148 AC: 22567 AN: 152056 Hom.: 1716 Cov.: 31

Gnomad AFR AF: 0.133

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.162

Gnomad ASJ AF: 0.147

Gnomad EAS AF: 0.0837

Gnomad SAS AF: 0.192

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.159

Gnomad OTH AF: 0.157

GnomAD4 exome AF: 0.182 AC: 452 AN: 2484 Hom.: 50 AF XY: 0.182 AC XY: 225 AN XY: 1238

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.189

Gnomad4 ASJ exome AF: 0.167

Gnomad4 EAS exome AF: 0.143

Gnomad4 SAS exome AF: 0.239

Gnomad4 FIN exome AF: 0.0946

Gnomad4 NFE exome AF: 0.186

Gnomad4 OTH exome AF: 0.138

GnomAD4 genome AF: 0.148 AC: 22580 AN: 152174 Hom.: 1716 Cov.: 31 AF XY: 0.147 AC XY: 10963 AN XY: 74406

Gnomad4 AFR AF: 0.133

Gnomad4 AMR AF: 0.162

Gnomad4 ASJ AF: 0.147

Gnomad4 EAS AF: 0.0835

Gnomad4 SAS AF: 0.192

Gnomad4 FIN AF: 0.134

Gnomad4 NFE AF: 0.159

Gnomad4 OTH AF: 0.159

Alfa AF: 0.159 Hom.: 934

Bravo AF: 0.147

Asia WGS AF: 0.144 AC: 502 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	0.84
DANN	Benign	0.52

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

Publications

LitVar

Other links and lift over

dbSNP: rs11741808; hg19: chr5-141004331;