NM_001378414.1:c.3174C>T
Variant names:
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2
The NM_001378414.1(HDAC4):c.3174C>T(p.Ala1058Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00103 in 1,613,840 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.00054 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0011 ( 2 hom. )
Consequence
HDAC4
NM_001378414.1 synonymous
NM_001378414.1 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.59
Genes affected
HDAC4 (HGNC:14063): (histone deacetylase 4) 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 class II of the histone deacetylase/acuc/apha family. It possesses histone deacetylase activity and represses transcription when tethered to a promoter. This protein does not bind DNA directly, but through transcription factors MEF2C and MEF2D. It seems to interact in a multiprotein complex with RbAp48 and HDAC3. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.67).
BP6
Variant 2-239053516-G-A is Benign according to our data. Variant chr2-239053516-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 195974.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=2}.
BP7
Synonymous conserved (PhyloP=-2.59 with no splicing effect.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000545 (83/152328) while in subpopulation NFE AF= 0.00097 (66/68022). AF 95% confidence interval is 0.000782. There are 0 homozygotes in gnomad4. There are 43 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High AC in GnomAd4 at 83 AD gene.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| HDAC4 | NM_001378414.1 | c.3174C>T | p.Ala1058Ala | synonymous_variant | Exon 26 of 27 | ENST00000543185.6 | NP_001365343.1 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| HDAC4 | ENST00000543185.6 | c.3174C>T | p.Ala1058Ala | synonymous_variant | Exon 26 of 27 | 5 | NM_001378414.1 | ENSP00000440481.3 | ||
| HDAC4 | ENST00000345617.7 | c.3159C>T | p.Ala1053Ala | synonymous_variant | Exon 26 of 27 | 1 | ENSP00000264606.3 | |||
| HDAC4 | ENST00000430200.1 | c.429C>T | p.Ala143Ala | synonymous_variant | Exon 3 of 4 | 3 | ENSP00000410551.1 | |||
| HDAC4 | ENST00000690129.1 | n.1188C>T | non_coding_transcript_exon_variant | Exon 9 of 10 |
Frequencies
GnomAD3 genomes 0.000545 AC: 83AN: 152210Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000467 AC: 117AN: 250582Hom.: 0 AF XY: 0.000413 AC XY: 56AN XY: 135692
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GnomAD4 exome AF: 0.00108 AC: 1574AN: 1461512Hom.: 2 Cov.: 32 AF XY: 0.00102 AC XY: 738AN XY: 727066
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GnomAD4 genome 0.000545 AC: 83AN: 152328Hom.: 0 Cov.: 33 AF XY: 0.000577 AC XY: 43AN XY: 74480
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:3
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:1Benign:2
Jul 01, 2022
CeGaT Center for Human Genetics Tuebingen
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
HDAC4: BP4, BP7 -
Dec 01, 2016
Eurofins Ntd Llc (ga)
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
Nov 10, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
HDAC4-related disorder Benign:1
Jul 29, 2019
PreventionGenetics, part of Exact Sciences
Significance: Likely benign
Review Status: no assertion criteria provided
Collection Method: clinical testing
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at