chr22-50246695-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_032019.6(HDAC10):​c.1555G>T​(p.Asp519Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,382 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D519H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

HDAC10
NM_032019.6 missense

Scores

6
13

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0880
Variant links:
Genes affected
HDAC10 (HGNC:18128): (histone deacetylase 10) The protein encoded by this gene belongs to the histone deacetylase family, members of which deacetylate lysine residues on the N-terminal part of the core histones. Histone deacetylation modulates chromatin structure, and plays an important role in transcriptional regulation, cell cycle progression, and developmental events. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2011]
MAPK12 (HGNC:6874): (mitogen-activated protein kinase 12) Activation of members of the mitogen-activated protein kinase family is a major mechanism for transduction of extracellular signals. Stress-activated protein kinases are one subclass of MAP kinases. The protein encoded by this gene functions as a signal transducer during differentiation of myoblasts to myotubes. [provided by RefSeq, Jul 2008]

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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 rank MANE Protein UniProt
HDAC10NM_032019.6 linkc.1555G>T p.Asp519Tyr missense_variant Exon 16 of 20 ENST00000216271.10 NP_114408.3 Q969S8-1
HDAC10NM_001159286.2 linkc.1495G>T p.Asp499Tyr missense_variant Exon 15 of 19 NP_001152758.1 Q969S8-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
HDAC10ENST00000216271.10 linkc.1555G>T p.Asp519Tyr missense_variant Exon 16 of 20 1 NM_032019.6 ENSP00000216271.5 Q969S8-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1459382
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
725996
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:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.13
BayesDel_addAF
Benign
-0.076
T
BayesDel_noAF
Benign
-0.35
CADD
Benign
16
DANN
Benign
0.95
DEOGEN2
Benign
0.057
T;T;.
Eigen
Benign
-0.28
Eigen_PC
Benign
-0.41
FATHMM_MKL
Benign
0.15
N
LIST_S2
Uncertain
0.89
D;D;D
M_CAP
Benign
0.017
T
MetaRNN
Uncertain
0.47
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.3
M;.;.
PrimateAI
Benign
0.36
T
PROVEAN
Uncertain
-2.5
N;N;N
REVEL
Benign
0.13
Sift
Uncertain
0.0040
D;D;D
Sift4G
Uncertain
0.0080
D;D;D
Polyphen
0.65
P;P;P
Vest4
0.57
MutPred
0.36
Loss of disorder (P = 0.021);.;.;
MVP
0.55
MPC
0.21
ClinPred
0.66
D
GERP RS
3.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.18
gMVP
0.56

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-50685124; API