X-72572742-G-T

Variant names:

• chrX-72572742-G-T
• rs147689487
• NM_018486.3:c.20C>A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_018486.3(HDAC8):​c.20C>A​(p.Pro7Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: not found (cov: 21)
  • Exomes 𝑓: 9.1e-7 (0 hom. 1 hem.)
  • Failed GnomAD Quality Control
• Consequence: HDAC8 NM_018486.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.72

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]

ENSG00000285547 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06464848).
• BP6: Variant X-72572742-G-T is Benign according to our data. Variant chrX-72572742-G-T is described in ClinVar as [Benign]. Clinvar id is 2903408.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HDAC8	NM_018486.3	c.20C>A	p.Pro7Gln	missense_variant	Exon 1 of 11	ENST00000373573.9	NP_060956.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HDAC8	ENST00000373573.9	c.20C>A	p.Pro7Gln	missense_variant	Exon 1 of 11	1	NM_018486.3	ENSP00000362674.3
ENSG00000285547	ENST00000648922.1	c.20C>A	p.Pro7Gln	missense_variant	Exon 1 of 12			ENSP00000497072.1

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD3 exomes AF: 0.00000546 AC: 1 AN: 183153 Hom.: 0 AF XY: 0.0000148 AC XY: 1 AN XY: 67603

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

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: 0.0000122

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 9.12e-7 AC: 1 AN: 1096802 Hom.: 0 Cov.: 30 AF XY: 0.00000276 AC XY: 1 AN XY: 362184

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 0.00000119

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 21

Bravo AF: 0.00000378

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Cornelia de Lange syndrome 5 Benign:1

Jun 18, 2023

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
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	18
DANN	Benign	0.96
DEOGEN2	Benign	0.027	.;T;T;.;.;.;.;.;.;.;.;T;.;T;.;.;.;.;.;.;.;.;T;.;.;.;.
FATHMM_MKL	Benign	0.31	N
LIST_S2	Uncertain	0.95	D;D;D;D;D;D;D;.;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
M_CAP	Benign	0.037	D
MetaRNN	Benign	0.065	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	1.4	.;.;L;.;.;.;L;.;.;.;.;.;.;.;.;.;.;.;.;L;.;.;.;L;.;L;L
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-1.4	.;N;N;.;.;.;N;.;.;.;.;N;.;N;.;.;.;N;.;N;.;.;N;N;.;N;N
REVEL	Benign	0.088
Sift	Uncertain	0.012	.;D;D;.;.;.;D;.;.;.;.;D;.;D;.;.;.;D;.;D;.;.;D;D;.;D;D
Sift4G	Uncertain	0.034	.;D;T;.;.;.;D;.;.;.;.;.;.;.;.;.;.;D;.;T;.;.;D;D;.;T;T
Polyphen		0.0	.;.;B;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.
Vest4		0.21, 0.20, 0.19, 0.22, 0.20, 0.24, 0.23, 0.22
MutPred		0.34		Loss of glycosylation at P7 (P = 0.057);Loss of glycosylation at P7 (P = 0.057);Loss of glycosylation at P7 (P = 0.057);Loss of glycosylation at P7 (P = 0.057);Loss of glycosylation at P7 (P = 0.057);Loss of glycosylation at P7 (P = 0.057);Loss of glycosylation at P7 (P = 0.057);Loss of glycosylation at P7 (P = 0.057);Loss of glycosylation at P7 (P = 0.057);Loss of glycosylation at P7 (P = 0.057);Loss of glycosylation at P7 (P = 0.057);Loss of glycosylation at P7 (P = 0.057);Loss of glycosylation at P7 (P = 0.057);Loss of glycosylation at P7 (P = 0.057);Loss of glycosylation at P7 (P = 0.057);Loss of glycosylation at P7 (P = 0.057);Loss of glycosylation at P7 (P = 0.057);Loss of glycosylation at P7 (P = 0.057);Loss of glycosylation at P7 (P = 0.057);Loss of glycosylation at P7 (P = 0.057);Loss of glycosylation at P7 (P = 0.057);Loss of glycosylation at P7 (P = 0.057);Loss of glycosylation at P7 (P = 0.057);Loss of glycosylation at P7 (P = 0.057);Loss of glycosylation at P7 (P = 0.057);Loss of glycosylation at P7 (P = 0.057);Loss of glycosylation at P7 (P = 0.057);
MVP		0.70
MPC		1.1
ClinPred		0.059	T
GERP RS		2.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.079
gMVP		0.50

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: rs147689487; hg19: chrX-71792592;