X-72330118-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_018486.3(HDAC8):c.1112-42A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00358 in 1,078,302 control chromosomes in the GnomAD database, including 92 homozygotes. There are 1,043 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.018 (46 hom., 554 hem., cov: 22)
  • Exomes 𝑓: 0.0019 (46 hom. 489 hem.)
• Consequence: HDAC8 NM_018486.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.08

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant X-72330118-T-C is Benign according to our data. Variant chrX-72330118-T-C is described in ClinVar as [Benign]. Clinvar id is 1270507.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0586 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HDAC8	NM_018486.3	c.1112-42A>G		intron_variant		ENST00000373573.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HDAC8	ENST00000373573.9	c.1112-42A>G		intron_variant		1	NM_018486.3	P4

Frequencies

GnomAD3 genomes AF: 0.0178 AC: 1991 AN: 112014 Hom.: 46 Cov.: 22 AF XY: 0.0163 AC XY: 556 AN XY: 34162

Gnomad AFR AF: 0.0611

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00808

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0167

Gnomad NFE AF: 0.000169

Gnomad OTH AF: 0.0106

GnomAD3 exomes AF: 0.00545 AC: 952 AN: 174680 Hom.: 28 AF XY: 0.00375 AC XY: 228 AN XY: 60802

Gnomad AFR exome AF: 0.0657

Gnomad AMR exome AF: 0.00346

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000574

Gnomad FIN exome AF: 0.0000633

Gnomad NFE exome AF: 0.000130

Gnomad OTH exome AF: 0.00137

GnomAD4 exome AF: 0.00194 AC: 1872 AN: 966233 Hom.: 46 Cov.: 20 AF XY: 0.00186 AC XY: 489 AN XY: 263553

Gnomad4 AFR exome AF: 0.0615

Gnomad4 AMR exome AF: 0.00375

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000795

Gnomad4 FIN exome AF: 0.0000495

Gnomad4 NFE exome AF: 0.0000622

Gnomad4 OTH exome AF: 0.00493

GnomAD4 genome AF: 0.0177 AC: 1988 AN: 112069 Hom.: 46 Cov.: 22 AF XY: 0.0162 AC XY: 554 AN XY: 34227

Gnomad4 AFR AF: 0.0609

Gnomad4 AMR AF: 0.00798

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000169

Gnomad4 OTH AF: 0.0105

Alfa AF: 0.00384 Hom.: 60

Bravo AF: 0.0202

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	11
Dann	Benign	0.76

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: rs2984288; hg19: chrX-71549968;