rs2530223

chr5-141634927-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_003883.4(HDAC3):c.165A>G(p.Gln55=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.613 in 1,613,510 control chromosomes in the GnomAD database, including 308,611 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 0.67 (35290 hom., cov: 31)
  • Exomes 𝑓: 0.61 (273321 hom.)
• Consequence: HDAC3 NM_003883.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.75

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]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP7: Synonymous conserved (PhyloP=1.75 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.84 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HDAC3	NM_003883.4	c.165A>G	p.Gln55=	synonymous_variant	3/15	ENST00000305264.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HDAC3	ENST00000305264.8	c.165A>G	p.Gln55=	synonymous_variant	3/15	1	NM_003883.4	P1

Frequencies

GnomAD3 genomes AF: 0.670 AC: 101711 AN: 151868 Hom.: 35233 Cov.: 31

Gnomad AFR AF: 0.847

Gnomad AMI AF: 0.459

Gnomad AMR AF: 0.694

Gnomad ASJ AF: 0.570

Gnomad EAS AF: 0.329

Gnomad SAS AF: 0.641

Gnomad FIN AF: 0.601

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.604

Gnomad OTH AF: 0.659

GnomAD3 exomes AF: 0.623 AC: 156603 AN: 251384 Hom.: 50727 AF XY: 0.617 AC XY: 83784 AN XY: 135868

Gnomad AFR exome AF: 0.854

Gnomad AMR exome AF: 0.767

Gnomad ASJ exome AF: 0.562

Gnomad EAS exome AF: 0.303

Gnomad SAS exome AF: 0.656

Gnomad FIN exome AF: 0.602

Gnomad NFE exome AF: 0.599

Gnomad OTH exome AF: 0.606

GnomAD4 exome AF: 0.607 AC: 887792 AN: 1461524 Hom.: 273321 Cov.: 49 AF XY: 0.608 AC XY: 441945 AN XY: 727062

Gnomad4 AFR exome AF: 0.852

Gnomad4 AMR exome AF: 0.763

Gnomad4 ASJ exome AF: 0.566

Gnomad4 EAS exome AF: 0.343

Gnomad4 SAS exome AF: 0.655

Gnomad4 FIN exome AF: 0.603

Gnomad4 NFE exome AF: 0.601

Gnomad4 OTH exome AF: 0.605

GnomAD4 genome AF: 0.670 AC: 101829 AN: 151986 Hom.: 35290 Cov.: 31 AF XY: 0.668 AC XY: 49614 AN XY: 74268

Gnomad4 AFR AF: 0.847

Gnomad4 AMR AF: 0.694

Gnomad4 ASJ AF: 0.570

Gnomad4 EAS AF: 0.329

Gnomad4 SAS AF: 0.639

Gnomad4 FIN AF: 0.601

Gnomad4 NFE AF: 0.604

Gnomad4 OTH AF: 0.660

Alfa AF: 0.619 Hom.: 38073

Bravo AF: 0.681

Asia WGS AF: 0.575 AC: 2001 AN: 3478

EpiCase AF: 0.589

EpiControl AF: 0.587

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
Cadd	Benign	11
Dann	Benign	0.83
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2530223; hg19: chr5-141014494; COSMIC: COSV51837168; COSMIC: COSV51837168;