Variant 7-18591594-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_178425.4(HDAC9):c.494C>G(p.Thr165Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000246 in 1,613,384 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00014 ( 1 hom. )

Consequence

HDAC9
NM_178425.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.55

Variant links:

Genes affected

HDAC9 (HGNC:14065): (histone deacetylase 9) 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 has sequence homology to members of the histone deacetylase family. This gene is orthologous to the Xenopus and mouse MITR genes. The MITR protein lacks the histone deacetylase catalytic domain. It represses MEF2 activity through recruitment of multicomponent corepressor complexes that include CtBP and HDACs. This encoded protein may play a role in hematopoiesis. Multiple alternatively spliced transcripts have been described for this gene but the full-length nature of some of them has not been determined. [provided by RefSeq, Jul 2008]

HDAC9 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0054661334).

BP6

Variant 7-18591594-C-G is Benign according to our data. Variant chr7-18591594-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 716079.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 186 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HDAC9	NM_178425.4 linkuse as main transcript	c.494C>G	p.Thr165Ser	missense_variant	5/26	ENST00000686413.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HDAC9	ENST00000686413.1 linkuse as main transcript	c.494C>G	p.Thr165Ser	missense_variant	5/26		NM_178425.4	P4	Q9UKV0-7

Frequencies

GnomAD3 genomes

AF:

0.00120

AC:

183

AN:

151914

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00412

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000656

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000301

AC:

AN:

248876

Hom.:

AF XY:

0.000259

AC XY:

AN XY:

135016

show subpopulations

Gnomad AFR exome

AF:

0.00407

Gnomad AMR exome

AF:

0.000320

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000886

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000144

AC:

211

AN:

1461352

Hom.:

Cov.:

AF XY:

0.000132

AC XY:

AN XY:

726954

show subpopulations

Gnomad4 AFR exome

AF:

0.00514

Gnomad4 AMR exome

AF:

0.000448

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.000215

GnomAD4 genome

AF:

0.00122

AC:

186

AN:

152032

Hom.:

Cov.:

AF XY:

0.00120

AC XY:

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.00418

Gnomad4 AMR

AF:

0.000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000293

Hom.:

Bravo

AF:

0.00141

ESP6500AA

AF:

0.00437

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000306

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Apr 24, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Benign

0.96

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.074

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.71

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

M_CAP

Benign

0.0025

MetaRNN

Benign

0.0055

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

MetaSVM

Benign

-1.1

MutationTaster

Benign

0.78

N;N;N;N;N;N;N;N;N;N

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.18

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

REVEL

Benign

0.11

Sift

Benign

0.80

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

Sift4G

Benign

0.94

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

Polyphen

0.0, 0.0020

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

Vest4

0.18

MutPred

0.18

.;.;Loss of glycosylation at T162 (P = 0.0676);Loss of glycosylation at T162 (P = 0.0676);Loss of glycosylation at T162 (P = 0.0676);.;.;Loss of glycosylation at T162 (P = 0.0676);.;.;.;

MVP

0.37

MPC

0.24

ClinPred

0.024

GERP RS

4.8

Varity_R

0.072

gMVP

0.089

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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