rs778696535

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_003883.4(HDAC3):​c.295G>C​(p.Gly99Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,716 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000027 ( 0 hom. )

Consequence

HDAC3
NM_003883.4 missense

Scores

13
5
1

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.72
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.921

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
HDAC3NM_003883.4 linkc.295G>C p.Gly99Arg missense_variant Exon 4 of 15 ENST00000305264.8 NP_003874.2 O15379-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
HDAC3ENST00000305264.8 linkc.295G>C p.Gly99Arg missense_variant Exon 4 of 15 1 NM_003883.4 ENSP00000302967.3 O15379-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000795
AC:
2
AN:
251472
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135912
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000176
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000274
AC:
4
AN:
1461716
Hom.:
0
Cov.:
32
AF XY:
0.00000275
AC XY:
2
AN XY:
727142
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000270
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.00000824
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.98
BayesDel_addAF
Pathogenic
0.39
D
BayesDel_noAF
Pathogenic
0.34
CADD
Pathogenic
30
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.60
D
Eigen
Pathogenic
0.93
Eigen_PC
Pathogenic
0.88
FATHMM_MKL
Pathogenic
1.0
D
LIST_S2
Pathogenic
0.99
D
M_CAP
Uncertain
0.18
D
MetaRNN
Pathogenic
0.92
D
MetaSVM
Uncertain
0.37
D
MutationAssessor
Pathogenic
2.9
M
PrimateAI
Pathogenic
0.95
D
PROVEAN
Pathogenic
-7.7
D
REVEL
Pathogenic
0.84
Sift
Pathogenic
0.0
D
Sift4G
Uncertain
0.026
D
Polyphen
1.0
D
Vest4
0.95
MutPred
0.75
Gain of solvent accessibility (P = 0.0971);
MVP
0.90
MPC
2.6
ClinPred
1.0
D
GERP RS
5.3
Varity_R
0.94
gMVP
0.91

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs778696535; hg19: chr5-141009679; API