rs2530223

Variant names:

• chr5-141634927-T-C
• rs2530223
• NM_003883.4:c.165A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_003883.4(HDAC3):​c.165A>G​(p.Gln55Gln) 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
• Publications: 43 publications found

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 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics
• neurodevelopmental disorder

  Inheritance: AD Classification: MODERATE Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003883.4. 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
	HDAC3	NM_003883.4	MANE Select	c.165A>G	p.Gln55Gln	synonymous	Exon 3 of 15	NP_003874.2
	HDAC3	NM_001355039.2		c.165A>G	p.Gln55Gln	synonymous	Exon 3 of 14	NP_001341968.1
	HDAC3	NM_001355040.2		c.-123+1621A>G		intron	N/A	NP_001341969.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HDAC3	ENST00000305264.8	TSL:1 MANE Select	c.165A>G	p.Gln55Gln	synonymous	Exon 3 of 15	ENSP00000302967.3	O15379-1
	HDAC3	ENST00000469550.6	TSL:1	n.238A>G		non_coding_transcript_exon	Exon 1 of 13
	HDAC3	ENST00000937593.1		c.165A>G	p.Gln55Gln	synonymous	Exon 3 of 15	ENSP00000607652.1

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

GnomAD2 exomes AF: 0.623 AC: 156603 AN: 251384 AF XY: 0.617

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 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

African (AFR) AF: 0.852 AC: 28530 AN: 33470

American (AMR) AF: 0.763 AC: 34114 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.566 AC: 14774 AN: 26122

East Asian (EAS) AF: 0.343 AC: 13632 AN: 39698

South Asian (SAS) AF: 0.655 AC: 56445 AN: 86234

European-Finnish (FIN) AF: 0.603 AC: 32206 AN: 53418

Middle Eastern (MID) AF: 0.592 AC: 3358 AN: 5674

European-Non Finnish (NFE) AF: 0.601 AC: 668192 AN: 1111822

Other (OTH) AF: 0.605 AC: 36541 AN: 60370

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

African (AFR) AF: 0.847 AC: 35137 AN: 41468

American (AMR) AF: 0.694 AC: 10596 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.570 AC: 1978 AN: 3472

East Asian (EAS) AF: 0.329 AC: 1697 AN: 5160

South Asian (SAS) AF: 0.639 AC: 3070 AN: 4806

European-Finnish (FIN) AF: 0.601 AC: 6346 AN: 10554

Middle Eastern (MID) AF: 0.578 AC: 170 AN: 294

European-Non Finnish (NFE) AF: 0.604 AC: 41028 AN: 67956

Other (OTH) AF: 0.660 AC: 1388 AN: 2102

Alfa AF: 0.629 Hom.: 94214

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	11
DANN	Benign	0.83
PhyloP100		1.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=91/9	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2530223; hg19: chr5-141014494; COSMIC: COSV51837168; COSMIC: COSV51837168;