2-239053523-TCGTTCTCGCAAGTCTGAGCCTCGATCAGAGAA-T
Variant summary
Our verdict is Pathogenic. The variant received 10 ACMG points: 10P and 0B. PVS1PM2
The NM_001378414.1(HDAC4):c.3135_3166delTTCTCTGATCGAGGCTCAGACTTGCGAGAACG(p.Ser1046ArgfsTer24) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_001378414.1 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Our verdict: Pathogenic. The variant received 10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
HDAC4 | NM_001378414.1 | c.3135_3166delTTCTCTGATCGAGGCTCAGACTTGCGAGAACG | p.Ser1046ArgfsTer24 | frameshift_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.3135_3166delTTCTCTGATCGAGGCTCAGACTTGCGAGAACG | p.Ser1046ArgfsTer24 | frameshift_variant | Exon 26 of 27 | 5 | NM_001378414.1 | ENSP00000440481.3 | ||
HDAC4 | ENST00000345617.7 | c.3120_3151delTTCTCTGATCGAGGCTCAGACTTGCGAGAACG | p.Ser1041ArgfsTer24 | frameshift_variant | Exon 26 of 27 | 1 | ENSP00000264606.3 | |||
HDAC4 | ENST00000430200.1 | c.390_421delTTCTCTGATCGAGGCTCAGACTTGCGAGAACG | p.Ser131fs | frameshift_variant | Exon 3 of 4 | 3 | ENSP00000410551.1 | |||
HDAC4 | ENST00000690129.1 | n.1149_1180delTTCTCTGATCGAGGCTCAGACTTGCGAGAACG | non_coding_transcript_exon_variant | Exon 9 of 10 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
not provided Uncertain:1
A variant of uncertain significance has been identified in the HDAC4 gene. The c.3120_3151del32 variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The c.3120_3151del32 variant is not observed in large population cohorts (Lek et al., 2016). The c.3120_3151del32 variant causes a frameshift starting with codon Serine 1041, changes this amino acid to a Arginine residue and creates a premature Stop codon at position 24 of the new reading frame, denoted p.Ser1041ArgfsX24. This variant is predicted to cause loss of normal protein function through protein truncation, as the last 44 amino acids are replaced by 23 incorrect amino acids. Based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at