dbSNP rs377020559: HDAC11:p.Arg213His (chr3-13502969-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_024827.4(HDAC11):c.638G>A(p.Arg213His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,460,662 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R213L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

HDAC11
NM_024827.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.34

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15690878).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HDAC11	NM_024827.4 link	c.638G>A	p.Arg213His	missense_variant	Exon 8 of 10	ENST00000295757.8	NP_079103.2	Q96DB2-1
HDAC11	NM_001136041.3 link	c.485G>A	p.Arg162His	missense_variant	Exon 8 of 10		NP_001129513.1	Q96DB2-2
HDAC11	NM_001330636.2 link	c.401G>A	p.Arg134His	missense_variant	Exon 5 of 7		NP_001317565.1	B5MCQ6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HDAC11	ENST00000295757.8 link	c.638G>A	p.Arg213His	missense_variant	Exon 8 of 10	1	NM_024827.4	ENSP00000295757.3		Q96DB2-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251336

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135838

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1460662

Hom.:

Cov.:

AF XY:

0.00000826

AC XY:

AN XY:

726708

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000540

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 06, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.638G>A (p.R213H) alteration is located in exon 8 (coding exon 8) of the HDAC11 gene. This alteration results from a G to A substitution at nucleotide position 638, causing the arginine (R) at amino acid position 213 to be replaced by a histidine (H). 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

0.098

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Benign

-0.24

CADD

Benign

DANN

Benign

0.78

DEOGEN2

Benign

0.015

T;T

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.027

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.46

.;T

M_CAP

Benign

0.0085

MetaRNN

Benign

0.16

T;T

MetaSVM

Benign

-0.95

PROVEAN

Benign

-0.26

N;.

REVEL

Benign

0.045

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.17

B;B

Vest4

0.34

MVP

0.52

ClinPred

0.97

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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