22-50249919-A-G

Position:

• chr22-50249919-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_032019.6(HDAC10):​c.435T>C​(p.Cys145Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.733 in 1,612,280 control chromosomes in the GnomAD database, including 437,584 homozygotes. 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 0.79 (48709 hom., cov: 32)
  • Exomes 𝑓: 0.73 (388875 hom.)
• Consequence: HDAC10 NM_032019.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.271

Genes affected

HDAC10 (HGNC:18128): (histone deacetylase 10) The protein encoded by this gene belongs to the histone deacetylase family, members of which deacetylate lysine residues on the N-terminal part of the core histones. Histone deacetylation modulates chromatin structure, and plays an important role in transcriptional regulation, cell cycle progression, and developmental events. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2011]

HDAC10 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP7: Synonymous conserved (PhyloP=-0.271 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.936 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HDAC10	NM_032019.6	c.435T>C	p.Cys145Cys	synonymous_variant	5/20	ENST00000216271.10	NP_114408.3
HDAC10	NM_001159286.2	c.435T>C	p.Cys145Cys	synonymous_variant	5/19		NP_001152758.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HDAC10	ENST00000216271.10	c.435T>C	p.Cys145Cys	synonymous_variant	5/20	1	NM_032019.6	ENSP00000216271.5

Frequencies

GnomAD3 genomes AF: 0.793 AC: 120421 AN: 151942 Hom.: 48651 Cov.: 32

Gnomad AFR AF: 0.944

Gnomad AMI AF: 0.627

Gnomad AMR AF: 0.813

Gnomad ASJ AF: 0.741

Gnomad EAS AF: 0.848

Gnomad SAS AF: 0.900

Gnomad FIN AF: 0.724

Gnomad MID AF: 0.737

Gnomad NFE AF: 0.700

Gnomad OTH AF: 0.771

GnomAD3 exomes AF: 0.782 AC: 195080 AN: 249318 Hom.: 77335 AF XY: 0.779 AC XY: 105349 AN XY: 135304

Gnomad AFR exome AF: 0.950

Gnomad AMR exome AF: 0.863

Gnomad ASJ exome AF: 0.729

Gnomad EAS exome AF: 0.855

Gnomad SAS exome AF: 0.895

Gnomad FIN exome AF: 0.734

Gnomad NFE exome AF: 0.707

Gnomad OTH exome AF: 0.755

GnomAD4 exome AF: 0.726 AC: 1060620 AN: 1460220 Hom.: 388875 Cov.: 52 AF XY: 0.729 AC XY: 529773 AN XY: 726428

Gnomad4 AFR exome AF: 0.949

Gnomad4 AMR exome AF: 0.857

Gnomad4 ASJ exome AF: 0.729

Gnomad4 EAS exome AF: 0.845

Gnomad4 SAS exome AF: 0.892

Gnomad4 FIN exome AF: 0.731

Gnomad4 NFE exome AF: 0.696

Gnomad4 OTH exome AF: 0.748

GnomAD4 genome AF: 0.793 AC: 120536 AN: 152060 Hom.: 48709 Cov.: 32 AF XY: 0.798 AC XY: 59280 AN XY: 74306

Gnomad4 AFR AF: 0.944

Gnomad4 AMR AF: 0.813

Gnomad4 ASJ AF: 0.741

Gnomad4 EAS AF: 0.847

Gnomad4 SAS AF: 0.901

Gnomad4 FIN AF: 0.724

Gnomad4 NFE AF: 0.700

Gnomad4 OTH AF: 0.768

Alfa AF: 0.726 Hom.: 63668

Bravo AF: 0.804

Asia WGS AF: 0.860 AC: 2993 AN: 3478

EpiCase AF: 0.705

EpiControl AF: 0.704

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.47
DANN	Benign	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: rs1555048; hg19: chr22-50688348;