X-72351602-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BS1 BS2

The NM_018486.3(HDAC8):c.1111+131C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00155 in 468,597 control chromosomes in the GnomAD database, including 1 homozygotes. There are 205 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 (0 hom., 41 hem., cov: 23)
  • Exomes 𝑓: 0.0017 (1 hom. 164 hem.)
• Consequence: HDAC8 NM_018486.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.52

Genes affected

HDAC8 (HGNC:13315): (histone deacetylase 8) 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 I of the histone deacetylase family. It catalyzes the deacetylation of lysine residues in the histone N-terminal tails and represses transcription in large multiprotein complexes with transcriptional co-repressors. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP6: Variant X-72351602-G-T is Benign according to our data. Variant chrX-72351602-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 2660912.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00118 (132/112331) while in subpopulation NFE AF= 0.0016 (85/53215). AF 95% confidence interval is 0.00132. There are 0 homozygotes in gnomad4. There are 41 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.
• BS2: High Hemizygotes in GnomAd at 41 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HDAC8	NM_018486.3	c.1111+131C>A		intron_variant		ENST00000373573.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HDAC8	ENST00000373573.9	c.1111+131C>A		intron_variant		1	NM_018486.3	P4

Frequencies

GnomAD3 genomes AF: 0.00118 AC: 132 AN: 112278 Hom.: 0 Cov.: 23 AF XY: 0.00119 AC XY: 41 AN XY: 34426

Gnomad AFR AF: 0.000356

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000469

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00506

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00160

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00167 AC: 595 AN: 356266 Hom.: 1 AF XY: 0.00139 AC XY: 164 AN XY: 117740

Gnomad4 AFR exome AF: 0.000390

Gnomad4 AMR exome AF: 0.000122

Gnomad4 ASJ exome AF: 0.0000955

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00446

Gnomad4 NFE exome AF: 0.00196

Gnomad4 OTH exome AF: 0.00131

GnomAD4 genome AF: 0.00118 AC: 132 AN: 112331 Hom.: 0 Cov.: 23 AF XY: 0.00119 AC XY: 41 AN XY: 34489

Gnomad4 AFR AF: 0.000355

Gnomad4 AMR AF: 0.000468

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00506

Gnomad4 NFE AF: 0.00160

Gnomad4 OTH AF: 0.00

Bravo AF: 0.000812

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Sep 01, 2022

HDAC8: BP4 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
Cadd	Benign	18
Dann	Benign	0.66

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

Other links and lift over

dbSNP: rs186172414; hg19: chrX-71571452;