chrX-72572062-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_018486.3(HDAC8):c.159G>A(p.Gln53Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0825 in 1,186,704 control chromosomes in the GnomAD database, including 17,200 homozygotes. There are 30,181 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 5302 hom., 7181 hem., cov: 21)

Exomes 𝑓: 0.067 ( 11898 hom. 23000 hem. )

Consequence

HDAC8
NM_018486.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.990

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP6

Variant X-72572062-C-T is Benign according to our data. Variant chrX-72572062-C-T is described in ClinVar as [Benign]. Clinvar id is 158659.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-72572062-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=0.99 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.651 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HDAC8	NM_018486.3 link	c.159G>A	p.Gln53Gln	synonymous_variant	Exon 2 of 11	ENST00000373573.9	NP_060956.1	Q9BY41-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HDAC8	ENST00000373573.9 link	c.159G>A	p.Gln53Gln	synonymous_variant	Exon 2 of 11	1	NM_018486.3	ENSP00000362674.3		Q9BY41-1
ENSG00000285547	ENST00000648922.1 link	c.159G>A	p.Gln53Gln	synonymous_variant	Exon 2 of 12			ENSP00000497072.1		A0A3B3IRV1

Frequencies

GnomAD3 genomes

AF:

0.233

AC:

25548

AN:

109860

Hom.:

5299

Cov.:

AF XY:

0.222

AC XY:

7154

AN XY:

32186

show subpopulations

Gnomad AFR

AF:

0.625

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.288

Gnomad ASJ

AF:

0.0315

Gnomad EAS

AF:

0.674

Gnomad SAS

AF:

0.215

Gnomad FIN

AF:

0.0215

Gnomad MID

AF:

0.0847

Gnomad NFE

AF:

0.0103

Gnomad OTH

AF:

0.212

GnomAD3 exomes

AF:

0.182

AC:

27603

AN:

151775

Hom.:

5914

AF XY:

0.125

AC XY:

5336

AN XY:

42789

show subpopulations

Gnomad AFR exome

AF:

0.631

Gnomad AMR exome

AF:

0.403

Gnomad ASJ exome

AF:

0.0260

Gnomad EAS exome

AF:

0.674

Gnomad SAS exome

AF:

0.194

Gnomad FIN exome

AF:

0.0249

Gnomad NFE exome

AF:

0.00930

Gnomad OTH exome

AF:

0.113

GnomAD4 exome

AF:

0.0671

AC:

72282

AN:

1076797

Hom.:

11898

Cov.:

AF XY:

0.0662

AC XY:

23000

AN XY:

347671

show subpopulations

Gnomad4 AFR exome

AF:

0.645

Gnomad4 AMR exome

AF:

0.392

Gnomad4 ASJ exome

AF:

0.0291

Gnomad4 EAS exome

AF:

0.684

Gnomad4 SAS exome

AF:

0.207

Gnomad4 FIN exome

AF:

0.0269

Gnomad4 NFE exome

AF:

0.00759

Gnomad4 OTH exome

AF:

0.111

GnomAD4 genome

AF:

0.233

AC:

25590

AN:

109907

Hom.:

5302

Cov.:

AF XY:

0.223

AC XY:

7181

AN XY:

32243

show subpopulations

Gnomad4 AFR

AF:

0.625

Gnomad4 AMR

AF:

0.288

Gnomad4 ASJ

AF:

0.0315

Gnomad4 EAS

AF:

0.674

Gnomad4 SAS

AF:

0.215

Gnomad4 FIN

AF:

0.0215

Gnomad4 NFE

AF:

0.0103

Gnomad4 OTH

AF:

0.213

Alfa

AF:

0.115

Hom.:

2013

Bravo

AF:

0.282

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Apr 04, 2017

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Sep 26, 2013

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Cornelia de Lange syndrome 5

Benign:2

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Aug 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Inborn genetic diseases

Benign:1

May 26, 2016

Ambry Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

7.6

DANN

Benign

0.54

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