rs527783582

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr22-50245530-A-G
• chr22-50245530-A-C

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>C​(p.Cys663Arg) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 968,700 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000024 (0 hom.)
• Consequence: HDAC10 NM_032019.6 missense, splice_region
• Scores: Splicing: ADA: 0.0001691
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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=0.08235976).

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>C	p.Cys663Arg	missense splice_region	Exon 20 of 20	NP_114408.3
	HDAC10	NM_001159286.2		c.1927T>C	p.Cys643Arg	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>C	p.Cys663Arg	missense splice_region	Exon 20 of 20	ENSP00000216271.5	Q969S8-1
	HDAC10	ENST00000349505.4	TSL:1	c.1927T>C	p.Cys643Arg	missense splice_region	Exon 19 of 19	ENSP00000343540.4	Q969S8-2
	HDAC10	ENST00000415993.5	TSL:1	n.*1508T>C		splice_region non_coding_transcript_exon	Exon 18 of 18	ENSP00000397517.1	Q08AP5

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152170 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000417 AC: 1 AN: 239568 AF XY: 0.00000766

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000556

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000245 AC: 2 AN: 816412 Hom.: 0 Cov.: 12 AF XY: 0.00000232 AC XY: 1 AN XY: 431664

African (AFR) AF: 0.00 AC: 0 AN: 21080

American (AMR) AF: 0.00 AC: 0 AN: 43474

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22002

East Asian (EAS) AF: 0.0000545 AC: 2 AN: 36730

South Asian (SAS) AF: 0.00 AC: 0 AN: 72920

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52040

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4468

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 524446

Other (OTH) AF: 0.00 AC: 0 AN: 39252

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152288 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74474

African (AFR) AF: 0.00 AC: 0 AN: 41564

American (AMR) AF: 0.00 AC: 0 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68006

Other (OTH) AF: 0.00 AC: 0 AN: 2112

ExAC AF: 0.00000825 AC: 1

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	10
DANN	Benign	0.56
DEOGEN2	Benign	0.26	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.044	N
LIST_S2	Benign	0.55	T
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.082	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.49	N
PhyloP100		-1.3
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.051
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.039	D
Polyphen		0.23	B
Vest4		0.12
MutPred		0.68		Gain of MoRF binding (P = 2e-04)
MVP		0.57
MPC		0.088
ClinPred		0.12	T
GERP RS		-6.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.31
gMVP		0.32
Mutation Taster		=92/8	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00017
dbscSNV1_RF	Benign	0.094
SpliceAI score (max)		0.010		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;