rs73000144
Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 1P and 20B. PP2BP4_StrongBP6_Very_StrongBS1BS2
The NM_001378414.1(HDAC4):c.958G>A(p.Val320Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00379 in 1,614,018 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V320A) has been classified as Likely benign.
Frequency
Consequence
NM_001378414.1 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -19 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HDAC4 | NM_001378414.1 | c.958G>A | p.Val320Ile | missense_variant | 9/27 | ENST00000543185.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HDAC4 | ENST00000543185.6 | c.958G>A | p.Val320Ile | missense_variant | 9/27 | 5 | NM_001378414.1 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.00319 AC: 485AN: 152236Hom.: 3 Cov.: 33
GnomAD3 exomes AF: 0.00304 AC: 761AN: 250556Hom.: 2 AF XY: 0.00326 AC XY: 442AN XY: 135512
GnomAD4 exome AF: 0.00385 AC: 5633AN: 1461664Hom.: 16 Cov.: 31 AF XY: 0.00388 AC XY: 2821AN XY: 727140
GnomAD4 genome ? AF: 0.00319 AC: 486AN: 152354Hom.: 3 Cov.: 33 AF XY: 0.00294 AC XY: 219AN XY: 74506
ClinVar
Submissions by phenotype
not provided Benign:5
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | May 05, 2021 | This variant is associated with the following publications: (PMID: 25335771) - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 15, 2024 | - - |
Likely benign, no assertion criteria provided | clinical testing | Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jun 01, 2024 | HDAC4: BP4, BS2 - |
Likely benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Nov 24, 2015 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at