Variant 3-13481393-A-C 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.150A>C(p.Lys50Asn) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,613,838 control chromosomes in the GnomAD database, with no homozygous occurrence. 2/3 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

HDAC11
NM_024827.4 missense, splice_region

Scores

Splicing: ADA: 0.9791

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.38

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:

HDAC11 (HGNC:):

HDAC11 links:

Genome browser will be placed here

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.150A>C	p.Lys50Asn	missense_variant, splice_region_variant	2/10	ENST00000295757.8	NP_079103.2	Q96DB2-1
HDAC11	NM_001136041.3 linkuse as main transcript	c.66A>C	p.Lys22Asn	missense_variant, splice_region_variant	2/10		NP_001129513.1	Q96DB2-2
HDAC11	NM_001330636.2 linkuse as main transcript	c.150A>C	p.Lys50Asn	missense_variant, splice_region_variant	2/7		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.150A>C	p.Lys50Asn	missense_variant, splice_region_variant	2/10	1	NM_024827.4	ENSP00000295757.3		Q96DB2-1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461698

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727138

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152140

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

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:

0.0000329

Hom.:

Bravo

AF:

0.0000113

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

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

Dec 03, 2024

The c.150A>C (p.K50N) alteration is located in exon 2 (coding exon 2) of the HDAC11 gene. This alteration results from a A to C substitution at nucleotide position 150, causing the lysine (K) at amino acid position 50 to be replaced by an asparagine (N). 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

0.83

BayesDel_addAF

Uncertain

0.020

BayesDel_noAF

Benign

-0.21

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.12

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

Eigen

Uncertain

0.33

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.94

.;D;D;D;D;D;D;D;D;D;D;D;D;D;D

M_CAP

Uncertain

0.13

MetaRNN

Uncertain

0.59

D;D;D;D;D;D;D;D;D;D;D;D;D;D;D

MetaSVM

Uncertain

0.048

MutationAssessor

Uncertain

2.3

.;M;.;.;.;.;.;.;.;.;.;.;.;.;.

PrimateAI

Uncertain

0.63

PROVEAN

Uncertain

-3.1

D;N;.;D;D;D;N;N;D;N;D;D;D;N;N

REVEL

Uncertain

0.34

Sift4G

Uncertain

0.026

D;.;D;.;.;.;.;T;T;T;T;T;T;T;T

Polyphen

1.0

D;B;D;.;.;.;.;B;.;.;.;.;.;.;.

Vest4

0.60

MutPred

0.46

.;Loss of ubiquitination at K50 (P = 0.0546);.;Loss of ubiquitination at K50 (P = 0.0546);Loss of ubiquitination at K50 (P = 0.0546);Loss of ubiquitination at K50 (P = 0.0546);Loss of ubiquitination at K50 (P = 0.0546);.;.;.;.;.;.;.;.;

MVP

0.80

MPC

0.93

ClinPred

0.99

GERP RS

4.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.61

gMVP

0.78

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

0.98

dbscSNV1_RF

Pathogenic

0.92

SpliceAI score (max)

0.020

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