rs147420530

Variant names:

• chrX-48802894-C-T
• rs147420530
• NM_006044.4:c.117C>T

Your query was ambiguous. Multiple possible variants found:

• chrX-48802894-C-T
• chrX-48802894-C-A
• chrX-48802894-C-G

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_006044.4(HDAC6):​c.117C>T​(p.Ala39Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000182 in 1,206,216 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 58 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 0.00020 (0 hom., 3 hem., cov: 23)
  • Exomes 𝑓: 0.00018 (0 hom. 55 hem.)
• Consequence: HDAC6 NM_006044.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.93
• Publications: 1 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: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant X-48802894-C-T is Benign according to our data. Variant chrX-48802894-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2660469.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.93 with no splicing effect.
• BS2: High Hemizygotes in GnomAd4 at 3 XL gene

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.117C>T	p.Ala39Ala	synonymous	Exon 3 of 29	NP_006035.2
	HDAC6	NM_001321225.2		c.159C>T	p.Ala53Ala	synonymous	Exon 4 of 30	NP_001308154.1	B4DZH6
	HDAC6	NM_001321226.2		c.117C>T	p.Ala39Ala	synonymous	Exon 3 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.117C>T	p.Ala39Ala	synonymous	Exon 3 of 29	ENSP00000334061.5	Q9UBN7-1
	HDAC6	ENST00000376619.7	TSL:1	c.117C>T	p.Ala39Ala	synonymous	Exon 3 of 29	ENSP00000365804.2	Q9UBN7-1
	HDAC6	ENST00000462730.5	TSL:1	c.117C>T	p.Ala39Ala	synonymous	Exon 3 of 6	ENSP00000496727.1	Q9BRX7

Frequencies

GnomAD3 genomes AF: 0.000197 AC: 22 AN: 111693 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000414

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000145 AC: 25 AN: 172671 AF XY: 0.000120

Gnomad AFR exome AF: 0.0000807

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000316

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000181 AC: 198 AN: 1094468 Hom.: 0 Cov.: 31 AF XY: 0.000153 AC XY: 55 AN XY: 360154

African (AFR) AF: 0.000152 AC: 4 AN: 26356

American (AMR) AF: 0.00 AC: 0 AN: 34803

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19320

East Asian (EAS) AF: 0.00 AC: 0 AN: 30112

South Asian (SAS) AF: 0.00 AC: 0 AN: 53408

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40285

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4128

European-Non Finnish (NFE) AF: 0.000227 AC: 191 AN: 840082

Other (OTH) AF: 0.0000653 AC: 3 AN: 45974

GnomAD4 genome AF: 0.000197 AC: 22 AN: 111748 Hom.: 0 Cov.: 23 AF XY: 0.0000884 AC XY: 3 AN XY: 33932

African (AFR) AF: 0.00 AC: 0 AN: 30802

American (AMR) AF: 0.00 AC: 0 AN: 10531

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2652

East Asian (EAS) AF: 0.00 AC: 0 AN: 3557

South Asian (SAS) AF: 0.00 AC: 0 AN: 2686

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5997

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 219

European-Non Finnish (NFE) AF: 0.000414 AC: 22 AN: 53095

Other (OTH) AF: 0.00 AC: 0 AN: 1522

Alfa AF: 0.000182 Hom.: 2

Bravo AF: 0.000170

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	5.9
DANN	Benign	0.85
PhyloP100		-2.9
PromoterAI		-0.030	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs147420530; hg19: chrX-48661301;