Variant 12-47791885-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_015401.5(HDAC7):c.1798C>T(p.Arg600Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000781 in 1,472,092 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000057 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000080 ( 0 hom. )

Consequence

HDAC7
NM_015401.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.12

Variant links:

Genes affected

HDAC7 (HGNC:14067): (histone deacetylase 7) 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 mouse HDAC7 gene whose protein promotes repression mediated via the transcriptional corepressor SMRT. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

HDAC7 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAd at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HDAC7	NM_015401.5 linkuse as main transcript	c.1798C>T	p.Arg600Trp	missense_variant	14/26	ENST00000080059.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HDAC7	ENST00000080059.12 linkuse as main transcript	c.1798C>T	p.Arg600Trp	missense_variant	14/26	1	NM_015401.5		Q8WUI4-5

Frequencies

GnomAD3 genomes

AF:

0.0000568

AC:

AN:

140956

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000516

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000145

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000114

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000461

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000829

AC:

AN:

241230

Hom.:

AF XY:

0.0000680

AC XY:

AN XY:

132300

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000293

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000279

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000143

Gnomad NFE exome

AF:

0.0000928

Gnomad OTH exome

AF:

0.000170

GnomAD4 exome

AF:

0.0000804

AC:

107

AN:

1331136

Hom.:

Cov.:

AF XY:

0.0000757

AC XY:

AN XY:

660138

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000246

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000139

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000116

Gnomad4 NFE exome

AF:

0.0000925

Gnomad4 OTH exome

AF:

0.0000388

GnomAD4 genome

AF:

0.0000568

AC:

AN:

140956

Hom.:

Cov.:

AF XY:

0.0000733

AC XY:

AN XY:

68206

show subpopulations

Gnomad4 AFR

AF:

0.0000516

Gnomad4 AMR

AF:

0.000145

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000114

Gnomad4 NFE

AF:

0.0000461

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000565

Hom.:

Bravo

AF:

0.0000378

ExAC

AF:

0.0000661

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000595

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 08, 2024

The c.1798C>T (p.R600W) alteration is located in exon 14 (coding exon 14) of the HDAC7 gene. This alteration results from a C to T substitution at nucleotide position 1798, causing the arginine (R) at amino acid position 600 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.58

BayesDel_addAF

Benign

-0.076

BayesDel_noAF

Uncertain

-0.040

Cadd

Uncertain

Dann

Uncertain

1.0

Eigen

Benign

-0.019

Eigen_PC

Benign

0.0051

FATHMM_MKL

Uncertain

0.77

LIST_S2

Pathogenic

0.99

D;D;D;D;D

M_CAP

Benign

0.063

MetaRNN

Uncertain

0.63

D;D;D;D;D

MetaSVM

Benign

-0.51

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Uncertain

0.71

PROVEAN

Uncertain

-4.0

D;D;D;D;D

REVEL

Uncertain

0.47

Sift

Uncertain

0.026

D;D;D;D;D

Sift4G

Uncertain

0.021

D;D;D;D;D

Polyphen

0.66

P;D;P;.;.

Vest4

0.68

MVP

0.71

MPC

0.95

ClinPred

0.19

GERP RS

2.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.41

gMVP

0.70

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