Variant chrX-72330118-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.08

Variant links:

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]

HDAC8 links:

ENSG00000285547 (HGNC:):

ENSG00000285547 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 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_multiple_submitters_no_conflicts, 2 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	Protein	UniProt
HDAC8	NM_018486.3 linkuse as main transcript	c.1112-42A>G		intron_variant		ENST00000373573.9	NP_060956.1	Q9BY41-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HDAC8	ENST00000373573.9 linkuse as main transcript	c.1112-42A>G		intron_variant		1	NM_018486.3	ENSP00000362674.3		Q9BY41-1
ENSG00000285547	ENST00000648922.1 linkuse as main transcript	c.1111+21615A>G		intron_variant				ENSP00000497072.1		A0A3B3IRV1

Frequencies

GnomAD3 genomes

AF:

0.0178

AC:

1991

AN:

112014

Hom.:

Cov.:

AF XY:

0.0163

AC XY:

556

AN XY:

34162

show subpopulations

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.:

AF XY:

0.00375

AC XY:

228

AN XY:

60802

show subpopulations

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.:

Cov.:

AF XY:

0.00186

AC XY:

489

AN XY:

263553

show subpopulations

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.:

Cov.:

AF XY:

0.0162

AC XY:

554

AN XY:

34227

show subpopulations

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.:

Bravo

AF:

0.0202

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over