Variant chr3-13504646-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_024827.4(HDAC11):c.1007A>G(p.Asn336Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000239 in 1,613,612 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00014 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00025 ( 0 hom. )

Consequence

HDAC11
NM_024827.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.101

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.036557287).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HDAC11	NM_024827.4 linkuse as main transcript	c.1007A>G	p.Asn336Ser	missense_variant	10/10	ENST00000295757.8	NP_079103.2	Q96DB2-1
HDAC11	NM_001136041.3 linkuse as main transcript	c.854A>G	p.Asn285Ser	missense_variant	10/10		NP_001129513.1	Q96DB2-2
HDAC11	NM_001330636.2 linkuse as main transcript	c.770A>G	p.Asn257Ser	missense_variant	7/7		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.1007A>G	p.Asn336Ser	missense_variant	10/10	1	NM_024827.4	ENSP00000295757.3		Q96DB2-1

Frequencies

GnomAD3 genomes

AF:

0.000145

AC:

AN:

152124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000250

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000247

AC:

AN:

251138

Hom.:

AF XY:

0.000272

AC XY:

AN XY:

135850

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.000397

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000449

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000248

AC:

363

AN:

1461488

Hom.:

Cov.:

AF XY:

0.000260

AC XY:

189

AN XY:

727080

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.000230

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000267

Gnomad4 FIN exome

AF:

0.0000189

Gnomad4 NFE exome

AF:

0.000286

Gnomad4 OTH exome

AF:

0.000166

GnomAD4 genome

AF:

0.000145

AC:

AN:

152124

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

74306

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000250

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000344

Hom.:

Bravo

AF:

0.000162

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000264

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000652

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 14, 2022

The c.1007A>G (p.N336S) alteration is located in exon 10 (coding exon 10) of the HDAC11 gene. This alteration results from a A to G substitution at nucleotide position 1007, causing the asparagine (N) at amino acid position 336 to be replaced by a serine (S). 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

0.081

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.55

CADD

Benign

6.6

DANN

Benign

0.93

DEOGEN2

Benign

0.054

T;T;T;T;.;.

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.74

FATHMM_MKL

Benign

0.027

LIST_S2

Benign

0.85

D;D;D;D;D;D

M_CAP

Benign

0.053

MetaRNN

Benign

0.037

T;T;T;T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.045

N;.;.;.;.;.

PrimateAI

Benign

0.40

PROVEAN

Benign

0.090

N;N;N;N;N;N

REVEL

Benign

0.12

Sift4G

Benign

0.92

.;.;.;.;T;T

Polyphen

0.0

B;.;.;.;.;.

Vest4

0.092

MVP

0.49

MPC

0.31

ClinPred

0.013

GERP RS

-2.2

Varity_R

0.098

gMVP

0.41

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