22-50245967-GAG-AAC

Variant names:

• chr22-50245967-GAG-AAC
• NM_032019.6:c.1774_1776delCTCinsGTT
• HDAC10 p.Leu592Val

Variant summary

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

The NM_032019.6(HDAC10):​c.1774_1776delCTCinsGTT​(p.Leu592Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. 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. L592F) has been classified as Uncertain significance.

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

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.1774_1776delCTCinsGTT	p.Leu592Val	missense	N/A	NP_114408.3
	HDAC10	NM_001159286.2		c.1714_1716delCTCinsGTT	p.Leu572Val	missense	N/A	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.1774_1776delCTCinsGTT	p.Leu592Val	missense	N/A	ENSP00000216271.5	Q969S8-1
	HDAC10	ENST00000349505.4	TSL:1	c.1714_1716delCTCinsGTT	p.Leu572Val	missense	N/A	ENSP00000343540.4	Q969S8-2
	HDAC10	ENST00000415993.5	TSL:1	n.*1295_*1297delCTCinsGTT		non_coding_transcript_exon	Exon 16 of 18	ENSP00000397517.1	Q08AP5

Frequencies

GnomAD3 genomes Cov.: 34

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.8

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr22-50684396;