chr22-50246351-C-T

Position:

• chr22-50246351-C-T

Variant summary

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

The NM_032019.6(HDAC10):​c.1597G>A​(p.Gly533Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 34)
• Consequence: HDAC10 NM_032019.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.40

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]

(HGNC:):

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]

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	UniProt
HDAC10	NM_032019.6	c.1597G>A	p.Gly533Ser	missense_variant	17/20	ENST00000216271.10
HDAC10	NM_001159286.2	c.1537G>A	p.Gly513Ser	missense_variant	16/19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HDAC10	ENST00000216271.10	c.1597G>A	p.Gly533Ser	missense_variant	17/20	1	NM_032019.6	P1
	ENST00000685176.2	n.1715C>T		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 34

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

Jun 06, 2023

The c.1597G>A (p.G533S) alteration is located in exon 17 (coding exon 17) of the HDAC10 gene. This alteration results from a G to A substitution at nucleotide position 1597, causing the glycine (G) at amino acid position 533 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	0.14
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	19
DANN	Benign	0.88
DEOGEN2	Benign	0.26	T;T;.
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.24	N
LIST_S2	Uncertain	0.89	D;D;D
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.12	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M;.;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.35	T
PROVEAN	Uncertain	-2.5	D;D;D
REVEL	Benign	0.16
Sift	Benign	0.15	T;T;T
Sift4G	Benign	0.32	T;T;T
Polyphen		0.30	B;P;B
Vest4		0.21
MutPred		0.43		Loss of ubiquitination at K534 (P = 0.0907);.;.;
MVP		0.57
MPC		0.27
ClinPred		0.53	D
GERP RS		3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.13
gMVP		0.33

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.25		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.25		Position offset: 22

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: chr22-50684780;