X-48802684-TCCTCAACTATGA-T

Variant names:

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

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1 PM2

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. 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

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]

ACMG classification

Verdict is Pathogenic. Variant got 10 ACMG points.

• PVS1: Start lost variant, no new inframe start found.
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HDAC6	NM_006044.4	c.-1_11delTATGACCTCAAC	p.Met1_Thr4del	start_lost, conservative_inframe_deletion	Exon 2 of 29	ENST00000334136.11	NP_006035.2
HDAC6	NM_006044.4	c.-1_11delTATGACCTCAAC		5_prime_UTR_variant	Exon 2 of 29	ENST00000334136.11	NP_006035.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HDAC6	ENST00000334136.11	c.-1_11delTATGACCTCAAC	p.Met1_Thr4del	start_lost, conservative_inframe_deletion	Exon 2 of 29	1	NM_006044.4	ENSP00000334061.5
HDAC6	ENST00000334136	c.-1_11delTATGACCTCAAC		5_prime_UTR_variant	Exon 2 of 29	1	NM_006044.4	ENSP00000334061.5

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

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Nov 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

HDAC6: PM2 -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-48661091;