chrX-48814749-G-A
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Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2
The NM_006044.4(HDAC6):c.999+9G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000232 in 1,209,410 control chromosomes in the GnomAD database, including 2 homozygotes. There are 68 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0012 ( 1 hom., 37 hem., cov: 23)
Exomes 𝑓: 0.00013 ( 1 hom. 31 hem. )
Consequence
HDAC6
NM_006044.4 intron
NM_006044.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.80
Genes affected
HDAC6 (HGNC:14064): (histone deacetylase 6) 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 contains an internal duplication of two catalytic domains which appear to function independently of each other. This protein possesses histone deacetylase activity and represses transcription. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.73).
BP6
Variant X-48814749-G-A is Benign according to our data. Variant chrX-48814749-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3057132.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High Hemizygotes in GnomAd4 at 37 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HDAC6 | NM_006044.4 | c.999+9G>A | intron_variant | ENST00000334136.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HDAC6 | ENST00000334136.11 | c.999+9G>A | intron_variant | 1 | NM_006044.4 | P2 |
Frequencies
GnomAD3 genomes AF: 0.00120 AC: 135AN: 112612Hom.: 1 Cov.: 23 AF XY: 0.00106 AC XY: 37AN XY: 34746
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GnomAD3 exomes AF: 0.000337 AC: 61AN: 180862Hom.: 0 AF XY: 0.000168 AC XY: 11AN XY: 65540
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GnomAD4 exome AF: 0.000131 AC: 144AN: 1096745Hom.: 1 Cov.: 31 AF XY: 0.0000856 AC XY: 31AN XY: 362229
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GnomAD4 genome AF: 0.00121 AC: 136AN: 112665Hom.: 1 Cov.: 23 AF XY: 0.00106 AC XY: 37AN XY: 34809
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
HDAC6-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 17, 2020 | 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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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at