X-72351717-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBS1BS2

The NM_018486.3(HDAC8):​c.1111+16C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000258 in 1,162,597 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 10 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 0 hem., cov: 24)
Exomes 𝑓: 0.000027 ( 0 hom. 10 hem. )

Consequence

HDAC8
NM_018486.3 intron

Scores

6

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.816
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.13712537).
BP6
Variant X-72351717-G-A is Benign according to our data. Variant chrX-72351717-G-A is described in ClinVar as [Benign]. Clinvar id is 1633109.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.0000267 (28/1050096) while in subpopulation AMR AF= 0.000257 (9/34979). AF 95% confidence interval is 0.000133. There are 0 homozygotes in gnomad4_exome. There are 10 alleles in male gnomad4_exome subpopulation. Median coverage is 22. This position pass quality control queck.
BS2
High Hemizygotes in GnomAdExome4 at 10 XL gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
HDAC8NM_018486.3 linkc.1111+16C>T intron_variant Intron 10 of 10 ENST00000373573.9 NP_060956.1 Q9BY41-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
HDAC8ENST00000373573.9 linkc.1111+16C>T intron_variant Intron 10 of 10 1 NM_018486.3 ENSP00000362674.3 Q9BY41-1
ENSG00000285547ENST00000648922.1 linkc.1111+16C>T intron_variant Intron 10 of 11 ENSP00000497072.1 A0A3B3IRV1

Frequencies

GnomAD3 genomes
AF:
0.0000178
AC:
2
AN:
112501
Hom.:
0
Cov.:
24
AF XY:
0.00
AC XY:
0
AN XY:
34657
show subpopulations
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:
0.0000375
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000624
AC:
11
AN:
176308
Hom.:
0
AF XY:
0.0000488
AC XY:
3
AN XY:
61434
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000374
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000228
GnomAD4 exome
AF:
0.0000267
AC:
28
AN:
1050096
Hom.:
0
Cov.:
22
AF XY:
0.0000306
AC XY:
10
AN XY:
326412
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000257
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000163
Gnomad4 OTH exome
AF:
0.000135
GnomAD4 genome
AF:
0.0000178
AC:
2
AN:
112501
Hom.:
0
Cov.:
24
AF XY:
0.00
AC XY:
0
AN XY:
34657
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000375
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000340

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Cornelia de Lange syndrome 5 Benign:1
Jan 27, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.76
CADD
Benign
7.2
DANN
Benign
0.75
FATHMM_MKL
Benign
0.17
N
LIST_S2
Benign
0.32
T;T
MetaRNN
Benign
0.14
T;T
GERP RS
1.4

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1039038766; hg19: chrX-71571567; API