chr22-50245530-A-C

Variant names:

• chr22-50245530-A-C
• rs527783582
• NM_032019.6:c.1987T>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032019.6(HDAC10):​c.1987T>G​(p.Cys663Gly) variant causes a missense, splice region 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. 18/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. 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. C663R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: HDAC10 NM_032019.6 missense, splice_region
• Scores: Splicing: ADA: 0.001983
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.27
• Publications: 1 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25121456).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032019.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HDAC10	NM_032019.6	MANE Select	c.1987T>G	p.Cys663Gly	missense splice_region	Exon 20 of 20	NP_114408.3
	HDAC10	NM_001159286.2		c.1927T>G	p.Cys643Gly	missense splice_region	Exon 19 of 19	NP_001152758.1	Q969S8-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HDAC10	ENST00000216271.10	TSL:1 MANE Select	c.1987T>G	p.Cys663Gly	missense splice_region	Exon 20 of 20	ENSP00000216271.5	Q969S8-1
	HDAC10	ENST00000349505.4	TSL:1	c.1927T>G	p.Cys643Gly	missense splice_region	Exon 19 of 19	ENSP00000343540.4	Q969S8-2
	HDAC10	ENST00000415993.5	TSL:1	n.*1508T>G		splice_region non_coding_transcript_exon	Exon 18 of 18	ENSP00000397517.1	Q08AP5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 12

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	9.5
DANN	Benign	0.52
DEOGEN2	Benign	0.26	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.036	N
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L
PhyloP100		-1.3
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.073
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.021	D
Polyphen		0.041	B
Vest4		0.068
MutPred		0.78		Gain of relative solvent accessibility (P = 0.0082)
MVP		0.50
MPC		0.063
ClinPred		0.40	T
GERP RS		-6.2
Varity_R		0.088
gMVP		0.27
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0020
dbscSNV1_RF	Benign	0.17
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

Other links and lift over

dbSNP: rs527783582; hg19: chr22-50683959;