chrX-48802684-TCCTCAACTATGA-T

Variant names:

• chrX-48802684-TCCTCAACTATGA-T
• NM_006044.4:c.-1_11delTATGACCTCAAC

Variant summary

Our verdict is Likely pathogenic. The variant received 8 ACMG points: 8P and 0B. PVS1

The NM_006044.4(HDAC6):​c.-1_11delTATGACCTCAAC​(p.Met1_Thr4del) variant causes a start lost, conservative inframe deletion 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 DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: HDAC6 NM_006044.4 start_lost, conservative_inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.39
• 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: Likely_pathogenic. The variant received 8 ACMG points.

• PVS1: Start lost variant, no new inframe start found.

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.-1_11delTATGACCTCAAC	p.Met1_Thr4del	start_lost conservative_inframe_deletion	Exon 2 of 29	NP_006035.2
	HDAC6	NM_006044.4	MANE Select	c.-1_11delTATGACCTCAAC		5_prime_UTR	Exon 2 of 29	NP_006035.2
	HDAC6	NM_001321226.2		c.-1_11delTATGACCTCAAC	p.Met1_Thr4del	start_lost conservative_inframe_deletion	Exon 2 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.-1_11delTATGACCTCAAC	p.Met1_Thr4del	start_lost conservative_inframe_deletion	Exon 2 of 29	ENSP00000334061.5	Q9UBN7-1
	HDAC6	ENST00000376619.7	TSL:1	c.-1_11delTATGACCTCAAC	p.Met1_Thr4del	start_lost conservative_inframe_deletion	Exon 2 of 29	ENSP00000365804.2	Q9UBN7-1
	HDAC6	ENST00000462730.5	TSL:1	c.-1_11delTATGACCTCAAC	p.Met1_Thr4del	start_lost conservative_inframe_deletion	Exon 2 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: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.4

Splicing

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

Other links and lift over

hg19: chrX-48661091;