Variant 3-13504190-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_024827.4(HDAC11):c.746A>G(p.His249Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 1,461,656 control chromosomes in the GnomAD database, with no homozygous occurrence. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

HDAC11
NM_024827.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.09

Variant links:

Genes affected

HDAC11 (HGNC:19086): (histone deacetylase 11) This gene encodes a class IV histone deacetylase. The encoded protein is localized to the nucleus and may be involved in regulating the expression of interleukin 10. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Apr 2009]

HDAC11 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HDAC11	NM_024827.4 linkuse as main transcript	c.746A>G	p.His249Arg	missense_variant	9/10	ENST00000295757.8	NP_079103.2	Q96DB2-1
HDAC11	NM_001136041.3 linkuse as main transcript	c.593A>G	p.His198Arg	missense_variant	9/10		NP_001129513.1	Q96DB2-2
HDAC11	NM_001330636.2 linkuse as main transcript	c.509A>G	p.His170Arg	missense_variant	6/7		NP_001317565.1	B5MCQ6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HDAC11	ENST00000295757.8 linkuse as main transcript	c.746A>G	p.His249Arg	missense_variant	9/10	1	NM_024827.4	ENSP00000295757.3		Q96DB2-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000797

AC:

AN:

251096

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135850

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000578

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000684

AC:

AN:

1461656

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

727114

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000540

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000189

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

Apr 09, 2024

The c.746A>G (p.H249R) alteration is located in exon 9 (coding exon 9) of the HDAC11 gene. This alteration results from a A to G substitution at nucleotide position 746, causing the histidine (H) at amino acid position 249 to be replaced by an arginine (R). 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

Benign

0.32

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Benign

0.87

DEOGEN2

Benign

0.13

T;T;T;T;.;.

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.63

FATHMM_MKL

Benign

0.066

LIST_S2

Benign

0.85

D;T;D;D;D;D

M_CAP

Benign

0.0046

MetaRNN

Uncertain

0.71

D;D;D;D;D;D

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.39

PROVEAN

Uncertain

-2.4

N;N;N;N;N;N

REVEL

Benign

0.17

Sift4G

Benign

0.13

.;.;.;.;T;T

Polyphen

0.0010

B;.;.;.;.;.

Vest4

0.44

MutPred

0.81

Loss of ubiquitination at K244 (P = 0.0935);.;.;.;.;.;

MVP

0.78

MPC

0.57

ClinPred

0.036

GERP RS

1.6

Varity_R

0.37

gMVP

0.92

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