chr5-141624764-A-G

Variant names:

• chr5-141624764-A-G
• rs11741808
• NM_003883.4:c.1217+444T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 20 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

ENSG00000228737 (HGNC:):

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 (SAS) allele frequency at 95% confidence interval = 0.181 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HDAC3	NM_003883.4	MANE Select	c.1217+444T>C		intron	N/A	NP_003874.2
	HDAC3	NM_001355040.2		c.758+444T>C		intron	N/A	NP_001341969.1
	HDAC3	NM_001355041.2		c.656+444T>C		intron	N/A	NP_001341970.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HDAC3	ENST00000305264.8	TSL:1 MANE Select	c.1217+444T>C		intron	N/A	ENSP00000302967.3
	HDAC3	ENST00000469550.6	TSL:1	n.1290+444T>C		intron	N/A
	ENSG00000228737	ENST00000422040.2	TSL:3	n.77-1083A>G		intron	N/A

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

African (AFR) AF: 0.00 AC: 0 AN: 30

American (AMR) AF: 0.189 AC: 31 AN: 164

Ashkenazi Jewish (ASJ) AF: 0.167 AC: 6 AN: 36

East Asian (EAS) AF: 0.143 AC: 2 AN: 14

South Asian (SAS) AF: 0.239 AC: 42 AN: 176

European-Finnish (FIN) AF: 0.0946 AC: 7 AN: 74

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4

European-Non Finnish (NFE) AF: 0.186 AC: 346 AN: 1856

Other (OTH) AF: 0.138 AC: 18 AN: 130

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

African (AFR) AF: 0.133 AC: 5530 AN: 41518

American (AMR) AF: 0.162 AC: 2468 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.147 AC: 511 AN: 3472

East Asian (EAS) AF: 0.0835 AC: 432 AN: 5176

South Asian (SAS) AF: 0.192 AC: 923 AN: 4816

European-Finnish (FIN) AF: 0.134 AC: 1423 AN: 10580

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.159 AC: 10811 AN: 68010

Other (OTH) AF: 0.159 AC: 337 AN: 2116

Alfa AF: 0.158 Hom.: 1258

Bravo AF: 0.147

Asia WGS AF: 0.144 AC: 502 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	0.84
DANN	Benign	0.52
PhyloP100		0.086
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11741808; hg19: chr5-141004331;