X-72572742-G-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_018486.3(HDAC8):c.20C>A(p.Pro7Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P7R) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 21)

Exomes 𝑓: 9.1e-7 ( 0 hom. 1 hem. )

Failed GnomAD Quality Control

Consequence

HDAC8
NM_018486.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.72

Publications

1 publications found

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 Gene-Disease associations (from GenCC):

Cornelia de Lange syndrome
Inheritance: AD, XL Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
Cornelia de Lange syndrome 5
Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
Wilson-Turner syndrome
Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

HDAC8 links:

ENSG00000285547 (HGNC:):

ENSG00000285547 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06464848).

BP6

Variant X-72572742-G-T is Benign according to our data. Variant chrX-72572742-G-T is described in ClinVar as Benign. ClinVar VariationId is 2903408.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HDAC8	NM_018486.3 link	c.20C>A	p.Pro7Gln	missense_variant	Exon 1 of 11	ENST00000373573.9	NP_060956.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HDAC8	ENST00000373573.9 link	c.20C>A	p.Pro7Gln	missense_variant	Exon 1 of 11	1	NM_018486.3	ENSP00000362674.3
ENSG00000285547	ENST00000648922.1 link	c.20C>A	p.Pro7Gln	missense_variant	Exon 1 of 12			ENSP00000497072.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000546

AC:

AN:

183153

AF XY:

0.0000148

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000122

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

9.12e-7

AC:

AN:

1096802

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

362184

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26374

American (AMR)

AF:

0.00

AC:

AN:

35198

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19373

East Asian (EAS)

AF:

0.00

AC:

AN:

30193

South Asian (SAS)

AF:

0.00

AC:

AN:

54108

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40434

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4134

European-Non Finnish (NFE)

AF:

0.00000119

AC:

AN:

840949

Other (OTH)

AF:

0.00

AC:

AN:

46039

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Cornelia de Lange syndrome 5

Benign:1

Jun 18, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.027

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

FATHMM_MKL

Benign

0.31

LIST_S2

Uncertain

0.95

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

M_CAP

Benign

0.037

MetaRNN

Benign

0.065

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

MetaSVM

Benign

-0.89

MutationAssessor

Benign

1.4

.;.;L;.;.;.;L;.;.;.;.;.;.;.;.;.;.;.;.;L;.;.;.;L;.;L;L

PhyloP100

1.7

PrimateAI

Benign

0.37

PROVEAN

Benign

-1.4

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

REVEL

Benign

0.088

Sift

Uncertain

0.012

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

Sift4G

Uncertain

0.034

.;D;T;.;.;.;D;.;.;.;.;.;.;.;.;.;.;D;.;T;.;.;D;D;.;T;T

Polyphen

0.0

.;.;B;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.

Vest4

0.21, 0.20, 0.19, 0.22, 0.20, 0.24, 0.23, 0.22

MutPred

0.34

Loss of glycosylation at P7 (P = 0.057);Loss of glycosylation at P7 (P = 0.057);Loss of glycosylation at P7 (P = 0.057);Loss of glycosylation at P7 (P = 0.057);Loss of glycosylation at P7 (P = 0.057);Loss of glycosylation at P7 (P = 0.057);Loss of glycosylation at P7 (P = 0.057);Loss of glycosylation at P7 (P = 0.057);Loss of glycosylation at P7 (P = 0.057);Loss of glycosylation at P7 (P = 0.057);Loss of glycosylation at P7 (P = 0.057);Loss of glycosylation at P7 (P = 0.057);Loss of glycosylation at P7 (P = 0.057);Loss of glycosylation at P7 (P = 0.057);Loss of glycosylation at P7 (P = 0.057);Loss of glycosylation at P7 (P = 0.057);Loss of glycosylation at P7 (P = 0.057);Loss of glycosylation at P7 (P = 0.057);Loss of glycosylation at P7 (P = 0.057);Loss of glycosylation at P7 (P = 0.057);Loss of glycosylation at P7 (P = 0.057);Loss of glycosylation at P7 (P = 0.057);Loss of glycosylation at P7 (P = 0.057);Loss of glycosylation at P7 (P = 0.057);Loss of glycosylation at P7 (P = 0.057);Loss of glycosylation at P7 (P = 0.057);Loss of glycosylation at P7 (P = 0.057);

MVP

0.70

MPC

1.1

ClinPred

0.059

GERP RS

2.9

PromoterAI

-0.041

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.079

gMVP

0.50

Mutation Taster

=291/9

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over