Variant 7-18647919-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_178425.4(HDAC9):c.1170A>T(p.Pro390Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0121 in 1,612,834 control chromosomes in the GnomAD database, including 209 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.011 ( 25 hom., cov: 33)

Exomes 𝑓: 0.012 ( 184 hom. )

Consequence

HDAC9
NM_178425.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0890

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:

HDAC9 (HGNC:):

HDAC9 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 7-18647919-A-T is Benign according to our data. Variant chr7-18647919-A-T is described in ClinVar as [Benign]. Clinvar id is 402926.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.089 with no splicing effect.

BS2

High AC in GnomAd4 at 1716 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HDAC9	NM_178425.4 linkuse as main transcript	c.1170A>T	p.Pro390Pro	synonymous_variant	10/26	ENST00000686413.1	NP_848512.1	Q9UKV0-7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HDAC9	ENST00000686413.1 linkuse as main transcript	c.1170A>T	p.Pro390Pro	synonymous_variant	10/26		NM_178425.4	ENSP00000509161.1		Q9UKV0-7

Frequencies

GnomAD3 genomes

AF:

0.0113

AC:

1718

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00232

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00681

Gnomad ASJ

AF:

0.0181

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.0605

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0115

Gnomad OTH

AF:

0.0124

GnomAD3 exomes

AF:

0.0119

AC:

2932

AN:

246840

Hom.:

AF XY:

0.0119

AC XY:

1592

AN XY:

133930

show subpopulations

Gnomad AFR exome

AF:

0.00209

Gnomad AMR exome

AF:

0.00406

Gnomad ASJ exome

AF:

0.0172

Gnomad EAS exome

AF:

0.0000565

Gnomad SAS exome

AF:

0.00220

Gnomad FIN exome

AF:

0.0516

Gnomad NFE exome

AF:

0.0120

Gnomad OTH exome

AF:

0.0126

GnomAD4 exome

AF:

0.0121

AC:

17728

AN:

1460536

Hom.:

184

Cov.:

AF XY:

0.0119

AC XY:

8619

AN XY:

726498

show subpopulations

Gnomad4 AFR exome

AF:

0.00200

Gnomad4 AMR exome

AF:

0.00442

Gnomad4 ASJ exome

AF:

0.0180

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00228

Gnomad4 FIN exome

AF:

0.0494

Gnomad4 NFE exome

AF:

0.0121

Gnomad4 OTH exome

AF:

0.0106

GnomAD4 genome

AF:

0.0113

AC:

1716

AN:

152298

Hom.:

Cov.:

AF XY:

0.0131

AC XY:

973

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.00231

Gnomad4 AMR

AF:

0.00680

Gnomad4 ASJ

AF:

0.0181

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.0605

Gnomad4 NFE

AF:

0.0115

Gnomad4 OTH

AF:

0.0118

Alfa

AF:

0.0112

Hom.:

Bravo

AF:

0.00733

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

6.4

DANN

Benign

0.44

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