rs3012642

chrX-72409062-A-GchrX-72409062-A-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
HDAC8	NM_018486.3	c.1005+52942T>C		intron_variant		ENST00000373573.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HDAC8	ENST00000373573.9	c.1005+52942T>C		intron_variant		1	NM_018486.3	P4

Frequencies

GnomAD3 genomes AF: 0.249 AC: 27705 AN: 111432 Hom.: 6100 Cov.: 23 AF XY: 0.241 AC XY: 8121 AN XY: 33646

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

Gnomad4 AFR AF: 0.675

Gnomad4 AMR AF: 0.262

Gnomad4 ASJ AF: 0.0404

Gnomad4 EAS AF: 0.739

Gnomad4 SAS AF: 0.254

Gnomad4 FIN AF: 0.0284

Gnomad4 NFE AF: 0.0104

Gnomad4 OTH AF: 0.218

Alfa AF: 0.0585 Hom.: 5502

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

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

LitVar

Other links and lift over

dbSNP: rs3012642; hg19: chrX-71628912;