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GeneBe

X-48806443-C-T

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_006044.4(HDAC6):c.513C>T(p.Tyr171=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00279 in 1,187,066 control chromosomes in the GnomAD database, including 5 homozygotes. There are 1,053 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0021 ( 1 hom., 58 hem., cov: 23)
Exomes 𝑓: 0.0029 ( 4 hom. 995 hem. )

Consequence

HDAC6
NM_006044.4 synonymous

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.842
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.58).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant X-48806443-C-T is Benign according to our data. Variant chrX-48806443-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 717434.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-48806443-C-T is described in Lovd as [Benign].
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.842 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Hemizygotes in GnomAd at 58 XL gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
HDAC6NM_006044.4 linkuse as main transcriptc.513C>T p.Tyr171= synonymous_variant 7/29 ENST00000334136.11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
HDAC6ENST00000334136.11 linkuse as main transcriptc.513C>T p.Tyr171= synonymous_variant 7/291 NM_006044.4 P2Q9UBN7-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00205
AC:
231
AN:
112481
Hom.:
1
Cov.:
23
AF XY:
0.00167
AC XY:
58
AN XY:
34633
show subpopulations
Gnomad AFR
AF:
0.00116
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000281
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000729
Gnomad FIN
AF:
0.000161
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00351
Gnomad OTH
AF:
0.00133
GnomAD3 exomes
AF:
0.00152
AC:
279
AN:
183355
Hom.:
0
AF XY:
0.00139
AC XY:
94
AN XY:
67793
show subpopulations
Gnomad AFR exome
AF:
0.000912
Gnomad AMR exome
AF:
0.000839
Gnomad ASJ exome
AF:
0.000134
Gnomad EAS exome
AF:
0.0000722
Gnomad SAS exome
AF:
0.000629
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00275
Gnomad OTH exome
AF:
0.00110
GnomAD4 exome
AF:
0.00286
AC:
3076
AN:
1074531
Hom.:
4
Cov.:
26
AF XY:
0.00291
AC XY:
995
AN XY:
342159
show subpopulations
Gnomad4 AFR exome
AF:
0.000617
Gnomad4 AMR exome
AF:
0.000938
Gnomad4 ASJ exome
AF:
0.000104
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000560
Gnomad4 FIN exome
AF:
0.000370
Gnomad4 NFE exome
AF:
0.00353
Gnomad4 OTH exome
AF:
0.00190
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00205
AC:
231
AN:
112535
Hom.:
1
Cov.:
23
AF XY:
0.00167
AC XY:
58
AN XY:
34697
show subpopulations
Gnomad4 AFR
AF:
0.00116
Gnomad4 AMR
AF:
0.000280
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000731
Gnomad4 FIN
AF:
0.000161
Gnomad4 NFE
AF:
0.00351
Gnomad4 OTH
AF:
0.00131
Alfa
AF:
0.00225
Hom.:
21
Bravo
AF:
0.00204
EpiCase
AF:
0.00398
EpiControl
AF:
0.00291

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

X-linked dominant chondrodysplasia, Chassaing-Lacombe type Benign:1
Likely benign, criteria provided, single submitterclinical testingFulgent Genetics, Fulgent GeneticsMar 02, 2022- -
not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.58
Cadd
Benign
5.5
Dann
Benign
0.46
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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.

Other links and lift over

dbSNP: rs73209760; hg19: chrX-48664850; COSMIC: COSV100491390; COSMIC: COSV100491390; API