Genetic Variant NM_032019.6:c.1894A>C (chr22-50245767-T-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_032019.6(HDAC10):c.1894A>C(p.Ser632Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,134 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/24 in silico tools predict a benign outcome for this variant. 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. S632G) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

HDAC10
NM_032019.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0460

Publications

0 publications found

Variant links:

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 links:

ENSG00000288871 (HGNC:):

ENSG00000288871 links:

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]

MAPK12 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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.1894A>C	p.Ser632Arg	missense	Exon 19 of 20	NP_114408.3
	HDAC10	NM_001159286.2		c.1834A>C	p.Ser612Arg	missense	Exon 18 of 19	NP_001152758.1	Q969S8-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HDAC10	ENST00000216271.10	TSL:1 MANE Select	c.1894A>C	p.Ser632Arg	missense	Exon 19 of 20	ENSP00000216271.5	Q969S8-1
HDAC10	ENST00000349505.4	TSL:1	c.1834A>C	p.Ser612Arg	missense	Exon 18 of 19	ENSP00000343540.4	Q969S8-2
HDAC10	ENST00000415993.5	TSL:1	n.*1415A>C		non_coding_transcript_exon	Exon 17 of 18	ENSP00000397517.1	Q08AP5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.87e-7

AC:

AN:

1455134

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

723450

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33248

American (AMR)

AF:

0.00

AC:

AN:

43852

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26004

East Asian (EAS)

AF:

0.00

AC:

AN:

39236

South Asian (SAS)

AF:

0.00

AC:

AN:

85250

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52272

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5748

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1109410

Other (OTH)

AF:

0.0000166

AC:

AN:

60114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.053

Eigen

Benign

0.020

Eigen_PC

Benign

-0.0037

FATHMM_MKL

Benign

0.34

LIST_S2

Benign

0.63

M_CAP

Benign

0.019

MetaRNN

Benign

0.21

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

PhyloP100

0.046

PrimateAI

Benign

0.39

PROVEAN

Benign

-2.1

REVEL

Benign

0.088

Sift

Benign

0.37

Sift4G

Benign

0.39

Polyphen

0.89

Vest4

0.31

MutPred

0.27

Loss of glycosylation at S632 (P = 0.0043)

MVP

0.66

MPC

0.24

ClinPred

0.67

GERP RS

4.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.069

gMVP

0.26

Mutation Taster

=93/7

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.35

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.35

Position offset: -7

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over