rs3012642

Variant names:

• chrX-72409062-A-G
• rs3012642
• NM_018486.3:c.1005+52942T>C

Your query was ambiguous. Multiple possible variants found:

• chrX-72409062-A-G
• chrX-72409062-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018486.3(HDAC8):​c.1005+52942T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.249 in 111,487 control chromosomes in the GnomAD database, including 6,101 homozygotes. There are 8,156 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.25 (6101 hom., 8156 hem., cov: 23)
• Consequence: HDAC8 NM_018486.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.275
• Publications: 2 publications found

Genes affected

HDAC8 (HGNC:13315): (histone deacetylase 8) 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 I of the histone deacetylase family. It catalyzes the deacetylation of lysine residues in the histone N-terminal tails and represses transcription in large multiprotein complexes with transcriptional co-repressors. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2009]

HDAC8 Gene-Disease associations (from GenCC):

• Cornelia de Lange syndrome

  Inheritance: AD, XL Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
• Cornelia de Lange syndrome 5

  Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• Wilson-Turner syndrome

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000285547 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.716 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HDAC8	NM_018486.3	c.1005+52942T>C		intron_variant	Intron 9 of 10	ENST00000373573.9	NP_060956.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HDAC8	ENST00000373573.9	c.1005+52942T>C		intron_variant	Intron 9 of 10	1	NM_018486.3	ENSP00000362674.3
ENSG00000285547	ENST00000648922.1	c.1005+52942T>C		intron_variant	Intron 9 of 11			ENSP00000497072.1

Frequencies

GnomAD3 genomes AF: 0.249 AC: 27705 AN: 111432 Hom.: 6100 Cov.: 23

Gnomad AFR AF: 0.675

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.262

Gnomad ASJ AF: 0.0404

Gnomad EAS AF: 0.740

Gnomad SAS AF: 0.253

Gnomad FIN AF: 0.0284

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0104

Gnomad OTH AF: 0.216

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.249 AC: 27751 AN: 111487 Hom.: 6101 Cov.: 23 AF XY: 0.242 AC XY: 8156 AN XY: 33711

African (AFR) AF: 0.675 AC: 20547 AN: 30444

American (AMR) AF: 0.262 AC: 2763 AN: 10543

Ashkenazi Jewish (ASJ) AF: 0.0404 AC: 107 AN: 2647

East Asian (EAS) AF: 0.739 AC: 2583 AN: 3493

South Asian (SAS) AF: 0.254 AC: 674 AN: 2658

European-Finnish (FIN) AF: 0.0284 AC: 174 AN: 6125

Middle Eastern (MID) AF: 0.0972 AC: 21 AN: 216

European-Non Finnish (NFE) AF: 0.0104 AC: 552 AN: 53161

Other (OTH) AF: 0.218 AC: 330 AN: 1517

Alfa AF: 0.113 Hom.: 14860

Bravo AF: 0.293

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	5.3
DANN	Benign	0.55
PhyloP100		0.28
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3012642; hg19: chrX-71628912;