Variant X-48803118-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_006044.4(HDAC6):c.223-10T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00038 in 1,204,093 control chromosomes in the GnomAD database, including 5 homozygotes. There are 162 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00071 ( 0 hom., 15 hem., cov: 23)

Exomes 𝑓: 0.00035 ( 5 hom. 147 hem. )

Consequence

HDAC6
NM_006044.4 intron

Scores

Splicing: ADA: 0.00002121

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0470

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant X-48803118-T-C is Benign according to our data. Variant chrX-48803118-T-C is described in ClinVar as [Benign]. Clinvar id is 712880.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 15 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HDAC6	NM_006044.4 link	c.223-10T>C		intron_variant		ENST00000334136.11	NP_006035.2	Q9UBN7-1A0A024QZ26Q9NSW6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HDAC6	ENST00000334136.11 link	c.223-10T>C		intron_variant		1	NM_006044.4	ENSP00000334061.5		Q9UBN7-1

Frequencies

GnomAD3 genomes

AF:

0.000686

AC:

AN:

110710

Hom.:

Cov.:

AF XY:

0.000364

AC XY:

AN XY:

32972

show subpopulations

Gnomad AFR

AF:

0.00217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000192

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000848

Gnomad SAS

AF:

0.00152

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000189

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000542

AC:

AN:

178940

Hom.:

AF XY:

0.000580

AC XY:

AN XY:

63802

show subpopulations

Gnomad AFR exome

AF:

0.00233

Gnomad AMR exome

AF:

0.000333

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00110

Gnomad SAS exome

AF:

0.00226

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000125

Gnomad OTH exome

AF:

0.000225

GnomAD4 exome

AF:

0.000347

AC:

379

AN:

1093336

Hom.:

Cov.:

AF XY:

0.000409

AC XY:

147

AN XY:

359038

show subpopulations

Gnomad4 AFR exome

AF:

0.00300

Gnomad4 AMR exome

AF:

0.000286

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00288

Gnomad4 SAS exome

AF:

0.00188

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000191

Gnomad4 OTH exome

AF:

0.00185

GnomAD4 genome

AF:

0.000713

AC:

AN:

110757

Hom.:

Cov.:

AF XY:

0.000454

AC XY:

AN XY:

33029

show subpopulations

Gnomad4 AFR

AF:

0.00227

Gnomad4 AMR

AF:

0.000192

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000851

Gnomad4 SAS

AF:

0.00152

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000189

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000712

Hom.:

Bravo

AF:

0.000801

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

6.9

DANN

Benign

0.69

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000021

dbscSNV1_RF

Benign

0.0020

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over