Variant X-72351778-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 0P and 3B. BP4BP6_Moderate

The NM_018486.3(HDAC8):c.1066C>T(p.Arg356Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000662 in 1,209,280 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 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 0.000018 ( 0 hom., 1 hem., cov: 23)

Exomes 𝑓: 0.0000055 ( 0 hom. 1 hem. )

Consequence

HDAC8
NM_018486.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 7.46

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.27192134).

BP6

Variant X-72351778-G-A is Benign according to our data. Variant chrX-72351778-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2718191.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HDAC8	NM_018486.3 linkuse as main transcript	c.1066C>T	p.Arg356Cys	missense_variant	10/11	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.1066C>T	p.Arg356Cys	missense_variant	10/11	1	NM_018486.3	ENSP00000362674.3		Q9BY41-1
ENSG00000285547	ENST00000648922.1 linkuse as main transcript	c.1066C>T	p.Arg356Cys	missense_variant	10/12			ENSP00000497072.1		A0A3B3IRV1

Frequencies

GnomAD3 genomes

AF:

0.0000178

AC:

AN:

112231

Hom.:

Cov.:

AF XY:

0.0000291

AC XY:

AN XY:

34403

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000369

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000219

AC:

AN:

182765

Hom.:

AF XY:

0.0000149

AC XY:

AN XY:

67325

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000365

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000724

Gnomad SAS exome

AF:

0.0000528

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000123

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000547

AC:

AN:

1096998

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

362384

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000284

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000594

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000178

AC:

AN:

112282

Hom.:

Cov.:

AF XY:

0.0000290

AC XY:

AN XY:

34464

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000370

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000188

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000189

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Cornelia de Lange syndrome 5

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 18, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Uncertain

0.13

BayesDel_noAF

Pathogenic

0.14

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.25

.;.;T;.;.;.;.;.;.;.;.;.;.;.

FATHMM_MKL

Uncertain

0.94

LIST_S2

Pathogenic

0.98

D;D;D;D;D;D;D;D;.;D;D;D;D;D

M_CAP

Uncertain

0.20

MetaRNN

Benign

0.27

T;T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Uncertain

0.12

MutationAssessor

Uncertain

2.8

.;.;M;.;.;.;.;.;.;.;.;.;.;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-1.2

.;.;N;.;.;.;.;N;.;.;.;.;.;.

REVEL

Uncertain

0.57

Sift

Benign

0.17

.;.;T;.;.;.;.;T;.;.;.;.;.;.

Sift4G

Benign

0.11

.;.;T;.;.;.;.;T;.;.;.;.;.;.

Polyphen

0.99

.;.;D;.;.;.;.;.;.;.;.;.;.;.

Vest4

0.20, 0.38

MutPred

0.41

Loss of disorder (P = 0.0236);.;Loss of disorder (P = 0.0236);Loss of disorder (P = 0.0236);Loss of disorder (P = 0.0236);.;.;.;Loss of disorder (P = 0.0236);.;Loss of disorder (P = 0.0236);.;Loss of disorder (P = 0.0236);.;

MVP

0.91

MPC

1.3

ClinPred

0.38

GERP RS

4.8

Varity_R

0.53

gMVP

0.94

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