Variant 3-13481293-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_024827.4(HDAC11):c.50C>A(p.Pro17Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,746 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

HDAC11
NM_024827.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.11

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.856

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HDAC11	NM_024827.4 linkuse as main transcript	c.50C>A	p.Pro17Gln	missense_variant	2/10	ENST00000295757.8	NP_079103.2	Q96DB2-1
HDAC11	NM_001330636.2 linkuse as main transcript	c.50C>A	p.Pro17Gln	missense_variant	2/7		NP_001317565.1	B5MCQ6
HDAC11	NM_001136041.3 linkuse as main transcript	c.-35C>A		5_prime_UTR_variant	2/10		NP_001129513.1	Q96DB2-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HDAC11	ENST00000295757.8 linkuse as main transcript	c.50C>A	p.Pro17Gln	missense_variant	2/10	1	NM_024827.4	ENSP00000295757.3		Q96DB2-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460746

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726698

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

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 26, 2022

The c.50C>A (p.P17Q) alteration is located in exon 2 (coding exon 2) of the HDAC11 gene. This alteration results from a C to A substitution at nucleotide position 50, causing the proline (P) at amino acid position 17 to be replaced by a glutamine (Q). 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

0.95

BayesDel_addAF

Pathogenic

0.32

BayesDel_noAF

Pathogenic

0.23

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.33

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

Eigen

Pathogenic

0.88

Eigen_PC

Pathogenic

0.83

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.97

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

M_CAP

Uncertain

0.22

MetaRNN

Pathogenic

0.86

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

MetaSVM

Uncertain

0.58

MutationAssessor

Pathogenic

3.3

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

PrimateAI

Uncertain

0.68

PROVEAN

Pathogenic

-6.3

D;N;D;D;D;D;D

REVEL

Pathogenic

0.80

Sift4G

Uncertain

0.0020

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

Polyphen

1.0

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

Vest4

0.81

MutPred

0.61

Gain of catalytic residue at P17 (P = 0.025);Gain of catalytic residue at P17 (P = 0.025);Gain of catalytic residue at P17 (P = 0.025);Gain of catalytic residue at P17 (P = 0.025);Gain of catalytic residue at P17 (P = 0.025);.;.;

MVP

0.99

MPC

1.2

ClinPred

1.0

GERP RS

5.3

Varity_R

0.87

gMVP

0.84

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