NM_006044.4:c.206_209delTGGG

Variant names:

• chrX-48802981-CGTGG-C
• NM_006044.4:c.206_209delTGGG

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP5

The NM_006044.4(HDAC6):​c.206_209delTGGG​(p.Val69AspfsTer7) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 23)
• Consequence: HDAC6 NM_006044.4 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 3.25
• Publications: 0 publications found

Genes affected

HDAC6 (HGNC:14064): (histone deacetylase 6) Histones play a critical role in transcriptional regulation, cell cycle progression, and developmental events. Histone acetylation/deacetylation alters chromosome structure and affects transcription factor access to DNA. The protein encoded by this gene belongs to class II of the histone deacetylase/acuc/apha family. It contains an internal duplication of two catalytic domains which appear to function independently of each other. This protein possesses histone deacetylase activity and represses transcription. [provided by RefSeq, Jul 2008]

HDAC6 Gene-Disease associations (from GenCC):

• X-linked dominant chondrodysplasia, Chassaing-Lacombe type

  Inheritance: XL Classification: MODERATE, SUPPORTIVE, LIMITED Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant X-48802981-CGTGG-C is Pathogenic according to our data. Variant chrX-48802981-CGTGG-C is described in ClinVar as Pathogenic. ClinVar VariationId is 3248614.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006044.4. 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
	HDAC6	NM_006044.4	MANE Select	c.206_209delTGGG	p.Val69AspfsTer7	frameshift	Exon 3 of 29	NP_006035.2
	HDAC6	NM_001321225.2		c.248_251delTGGG	p.Val83AspfsTer7	frameshift	Exon 4 of 30	NP_001308154.1	B4DZH6
	HDAC6	NM_001321226.2		c.206_209delTGGG	p.Val69AspfsTer7	frameshift	Exon 3 of 29	NP_001308155.1	Q9UBN7-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HDAC6	ENST00000334136.11	TSL:1 MANE Select	c.206_209delTGGG	p.Val69AspfsTer7	frameshift	Exon 3 of 29	ENSP00000334061.5	Q9UBN7-1
	HDAC6	ENST00000376619.7	TSL:1	c.206_209delTGGG	p.Val69AspfsTer7	frameshift	Exon 3 of 29	ENSP00000365804.2	Q9UBN7-1
	HDAC6	ENST00000462730.5	TSL:1	c.206_209delTGGG	p.Val69AspfsTer7	frameshift	Exon 3 of 6	ENSP00000496727.1	Q9BRX7

Frequencies

GnomAD3 genomes Cov.: 23

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

GnomAD4 genome Cov.: 23

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
1	-	-	X-linked dominant chondrodysplasia, Chassaing-Lacombe type (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.3

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

Other links and lift over

hg19: chrX-48661388;