Variant chr3-13483464-A-T 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.152A>T(p.Glu51Val) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,094 control chromosomes in the GnomAD database, with no homozygous occurrence. 2/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

HDAC11
NM_024827.4 missense, splice_region

Scores

Splicing: ADA: 0.8625

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.53

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.152A>T	p.Glu51Val	missense_variant, splice_region_variant	3/10	ENST00000295757.8	NP_079103.2	Q96DB2-1
HDAC11	NM_001136041.3 linkuse as main transcript	c.68A>T	p.Glu23Val	missense_variant, splice_region_variant	3/10		NP_001129513.1	Q96DB2-2
HDAC11	NM_001330636.2 linkuse as main transcript	c.152A>T	p.Glu51Val	missense_variant, splice_region_variant	3/7		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.152A>T	p.Glu51Val	missense_variant, splice_region_variant	3/10	1	NM_024827.4	ENSP00000295757.3		Q96DB2-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152094

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152094

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74298

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

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

Sep 20, 2024

The c.152A>T (p.E51V) alteration is located in exon 3 (coding exon 3) of the HDAC11 gene. This alteration results from a A to T substitution at nucleotide position 152, causing the glutamic acid (E) at amino acid position 51 to be replaced by a valine (V). 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

Uncertain

0.43

BayesDel_addAF

Pathogenic

0.23

BayesDel_noAF

Uncertain

0.090

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.12

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

Eigen

Uncertain

0.62

Eigen_PC

Uncertain

0.65

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.91

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

M_CAP

Uncertain

0.18

MetaRNN

Uncertain

0.63

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

MetaSVM

Uncertain

0.10

MutationAssessor

Uncertain

2.9

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

PrimateAI

Uncertain

0.49

PROVEAN

Pathogenic

-4.8

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

REVEL

Uncertain

0.56

Sift4G

Uncertain

0.011

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

Polyphen

1.0

D;P;D;.;.;.;P;.;.;.;.;.;.;.

Vest4

0.57

MutPred

0.51

.;Loss of disorder (P = 0.0236);.;Loss of disorder (P = 0.0236);Loss of disorder (P = 0.0236);Loss of disorder (P = 0.0236);.;.;.;.;.;.;.;.;

MVP

0.88

MPC

1.2

ClinPred

1.0

GERP RS

5.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.63

gMVP

0.76

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.86

dbscSNV1_RF

Benign

0.59

SpliceAI score (max)

0.24

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.24

Position offset: 22

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