Genetic Variant NM_006044.4:c.2659T>C (chrX-48823058-T-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_006044.4(HDAC6):c.2659T>C(p.Phe887Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 22)

Consequence

HDAC6
NM_006044.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.767

Publications

0 publications found

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 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

HDAC6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.047596365).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HDAC6	NM_006044.4	MANE Select	c.2659T>C	p.Phe887Leu	missense	Exon 25 of 29	NP_006035.2
HDAC6	NM_001321225.2		c.2701T>C	p.Phe901Leu	missense	Exon 26 of 30	NP_001308154.1	B4DZH6
HDAC6	NM_001321226.2		c.2659T>C	p.Phe887Leu	missense	Exon 25 of 29	NP_001308155.1	Q9UBN7-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HDAC6	ENST00000334136.11	TSL:1 MANE Select	c.2659T>C	p.Phe887Leu	missense	Exon 25 of 29	ENSP00000334061.5	Q9UBN7-1
HDAC6	ENST00000376619.7	TSL:1	c.2659T>C	p.Phe887Leu	missense	Exon 25 of 29	ENSP00000365804.2	Q9UBN7-1
HDAC6	ENST00000477528.5	TSL:1	n.3473T>C		non_coding_transcript_exon	Exon 24 of 28

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.86

(source)

DANN

Benign

0.86

DEOGEN2

Benign

0.094

FATHMM_MKL

Benign

0.055

LIST_S2

Benign

0.63

M_CAP

Benign

0.0073

MetaRNN

Benign

0.048

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.34

PhyloP100

-0.77

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.63

REVEL

Benign

0.047

Sift

Benign

0.99

Sift4G

Benign

0.62

Polyphen

0.0010

Vest4

0.054

MutPred

0.32

Gain of MoRF binding (P = 0.1451)

MVP

0.27

MPC

0.069

ClinPred

0.033

GERP RS

-1.8

PromoterAI

-0.013

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.043

gMVP

0.21

Mutation Taster

=99/1

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over