22-50245969-G-C

Variant names:

• chr22-50245969-G-C
• NM_032019.6:c.1774C>G

Variant summary

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

The NM_032019.6(HDAC10):​c.1774C>G​(p.Leu592Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000275 in 1,455,242 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: HDAC10 NM_032019.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.79

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]

ENSG00000288871 (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 rank	MANE	Protein	UniProt
HDAC10	NM_032019.6	c.1774C>G	p.Leu592Val	missense_variant	Exon 18 of 20	ENST00000216271.10	NP_114408.3
HDAC10	NM_001159286.2	c.1714C>G	p.Leu572Val	missense_variant	Exon 17 of 19		NP_001152758.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HDAC10	ENST00000216271.10	c.1774C>G	p.Leu592Val	missense_variant	Exon 18 of 20	1	NM_032019.6	ENSP00000216271.5

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000275 AC: 4 AN: 1455242 Hom.: 0 Cov.: 35 AF XY: 0.00000276 AC XY: 2 AN XY: 723570

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000360

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T;T;.
Eigen	Uncertain	0.21
Eigen_PC	Benign	0.12
FATHMM_MKL	Benign	0.55	D
LIST_S2	Uncertain	0.86	D;D;D
M_CAP	Benign	0.017	T
MetaRNN	Uncertain	0.50	T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.5	M;.;.
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-1.7	N;N;N
REVEL	Benign	0.17
Sift	Benign	0.044	D;D;D
Sift4G	Benign	0.49	T;D;D
Polyphen		1.0	D;D;D
Vest4		0.40
MutPred		0.47		Gain of catalytic residue at L592 (P = 0.0073);.;.;
MVP		0.51
MPC		0.26
ClinPred		0.85	D
GERP RS		3.2
Varity_R		0.082
gMVP		0.45

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: chr22-50684398;