Genetic Variant ENST00000432645.6:c.3030C>T (chr7-18954247-C-T) – ACMG Classification: Benign (-15 pts)

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The ENST00000432645.6(HDAC9):c.3030C>T(p.Phe1010Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.76 in 1,368,696 control chromosomes in the GnomAD database, including 395,978 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.77 ( 45700 hom., cov: 32)

Exomes 𝑓: 0.76 ( 350278 hom. )

Consequence

HDAC9
ENST00000432645.6 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.337

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 -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 7-18954247-C-T is Benign according to our data. Variant chr7-18954247-C-T is described in ClinVar as [Benign]. Clinvar id is 402925.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.337 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.802 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HDAC9	NM_178425.4 link	c.3022+17C>T		intron_variant	Intron 24 of 25	ENST00000686413.1	NP_848512.1	Q9UKV0-7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HDAC9	ENST00000686413.1 link	c.3022+17C>T		intron_variant	Intron 24 of 25		NM_178425.4	ENSP00000509161.1		Q9UKV0-7

Frequencies

GnomAD3 genomes

AF:

0.775

AC:

117682

AN:

151872

Hom.:

45654

Cov.:

show subpopulations

Gnomad AFR

AF:

0.809

Gnomad AMI

AF:

0.702

Gnomad AMR

AF:

0.809

Gnomad ASJ

AF:

0.767

Gnomad EAS

AF:

0.715

Gnomad SAS

AF:

0.780

Gnomad FIN

AF:

0.765

Gnomad MID

AF:

0.759

Gnomad NFE

AF:

0.754

Gnomad OTH

AF:

0.762

GnomAD3 exomes

AF:

0.776

AC:

122720

AN:

158116

Hom.:

47771

AF XY:

0.774

AC XY:

64314

AN XY:

83106

show subpopulations

Gnomad AFR exome

AF:

0.805

Gnomad AMR exome

AF:

0.872

Gnomad ASJ exome

AF:

0.772

Gnomad EAS exome

AF:

0.713

Gnomad SAS exome

AF:

0.779

Gnomad FIN exome

AF:

0.761

Gnomad NFE exome

AF:

0.752

Gnomad OTH exome

AF:

0.758

GnomAD4 exome

AF:

0.758

AC:

921878

AN:

1216708

Hom.:

350278

Cov.:

AF XY:

0.759

AC XY:

461809

AN XY:

608528

show subpopulations

Gnomad4 AFR exome

AF:

0.802

Gnomad4 AMR exome

AF:

0.862

Gnomad4 ASJ exome

AF:

0.779

Gnomad4 EAS exome

AF:

0.704

Gnomad4 SAS exome

AF:

0.782

Gnomad4 FIN exome

AF:

0.759

Gnomad4 NFE exome

AF:

0.752

Gnomad4 OTH exome

AF:

0.760

GnomAD4 genome

AF:

0.775

AC:

117786

AN:

151988

Hom.:

45700

Cov.:

AF XY:

0.778

AC XY:

57762

AN XY:

74286

show subpopulations

Gnomad4 AFR

AF:

0.809

Gnomad4 AMR

AF:

0.809

Gnomad4 ASJ

AF:

0.767

Gnomad4 EAS

AF:

0.715

Gnomad4 SAS

AF:

0.779

Gnomad4 FIN

AF:

0.765

Gnomad4 NFE

AF:

0.754

Gnomad4 OTH

AF:

0.765

Alfa

AF:

0.764

Hom.:

14897

Bravo

AF:

0.778

Asia WGS

AF:

0.761

AC:

2636

AN:

3466

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

-0.86

CADD

Benign

2.4

DANN

Benign

0.63

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