22-50246309-G-C

Position:

• chr22-50246309-G-C

Variant summary

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

The NM_032019.6(HDAC10):​c.1639C>G​(p.Pro547Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: HDAC10 NM_032019.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.37

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]

HDAC10 (HGNC:):

ACMG classification

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
HDAC10	NM_032019.6	c.1639C>G	p.Pro547Ala	missense_variant	17/20	ENST00000216271.10	NP_114408.3
HDAC10	NM_001159286.2	c.1579C>G	p.Pro527Ala	missense_variant	16/19		NP_001152758.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HDAC10	ENST00000216271.10	c.1639C>G	p.Pro547Ala	missense_variant	17/20	1	NM_032019.6	ENSP00000216271.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 18, 2023

The c.1639C>G (p.P547A) alteration is located in exon 17 (coding exon 17) of the HDAC10 gene. This alteration results from a C to G substitution at nucleotide position 1639, causing the proline (P) at amino acid position 547 to be replaced by an alanine (A). 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	0.083
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	17
DANN	Benign	0.68
DEOGEN2	Benign	0.082	T;T;.
Eigen	Benign	0.11
Eigen_PC	Benign	0.072
FATHMM_MKL	Benign	0.71	D
LIST_S2	Uncertain	0.87	D;D;D
M_CAP	Benign	0.011	T
MetaRNN	Uncertain	0.65	D;D;D
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.9	M;.;.
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-2.2	N;N;N
REVEL	Benign	0.20
Sift	Benign	0.46	T;T;T
Sift4G	Benign	0.85	T;T;T
Polyphen		0.58	P;D;P
Vest4		0.44
MutPred		0.78		Gain of catalytic residue at P547 (P = 0.0394);.;.;
MVP		0.66
MPC		0.35
ClinPred		0.31	T
GERP RS		3.5
Varity_R		0.046
gMVP		0.28

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: chr22-50684738;