chr22-50245229-G-C

Position:

• chr22-50245229-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_032019.6(HDAC10):​c.*278C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0212 in 571,458 control chromosomes in the GnomAD database, including 427 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.015 (65 hom., cov: 32)
  • Exomes 𝑓: 0.023 (362 hom.)
• Consequence: HDAC10 NM_032019.6 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.03

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BP6: Variant 22-50245229-G-C is Benign according to our data. Variant chr22-50245229-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 1193116.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.114 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HDAC10	NM_032019.6	c.*278C>G		3_prime_UTR_variant	20/20	ENST00000216271.10
HDAC10	NM_001159286.2	c.*278C>G		3_prime_UTR_variant	19/19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HDAC10	ENST00000216271.10	c.*278C>G		3_prime_UTR_variant	20/20	1	NM_032019.6	P1
	ENST00000685176.2	n.593G>C		non_coding_transcript_exon_variant	1/1
HDAC10	ENST00000415993.5	c.*1809C>G		3_prime_UTR_variant, NMD_transcript_variant	18/18	1
HDAC10	ENST00000626012.2	c.*1900C>G		3_prime_UTR_variant	19/19	5

Frequencies

GnomAD3 genomes AF: 0.0151 AC: 2299 AN: 152058 Hom.: 66 Cov.: 32

Gnomad AFR AF: 0.00254

Gnomad AMI AF: 0.0285

Gnomad AMR AF: 0.0242

Gnomad ASJ AF: 0.0115

Gnomad EAS AF: 0.122

Gnomad SAS AF: 0.0574

Gnomad FIN AF: 0.00566

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.0111

Gnomad OTH AF: 0.0167

GnomAD4 exome AF: 0.0235 AC: 9847 AN: 419282 Hom.: 362 Cov.: 0 AF XY: 0.0246 AC XY: 5454 AN XY: 221932

Gnomad4 AFR exome AF: 0.00268

Gnomad4 AMR exome AF: 0.0316

Gnomad4 ASJ exome AF: 0.0131

Gnomad4 EAS exome AF: 0.134

Gnomad4 SAS exome AF: 0.0481

Gnomad4 FIN exome AF: 0.00849

Gnomad4 NFE exome AF: 0.0106

Gnomad4 OTH exome AF: 0.0164

GnomAD4 genome AF: 0.0151 AC: 2295 AN: 152176 Hom.: 65 Cov.: 32 AF XY: 0.0165 AC XY: 1230 AN XY: 74400

Gnomad4 AFR AF: 0.00253

Gnomad4 AMR AF: 0.0241

Gnomad4 ASJ AF: 0.0115

Gnomad4 EAS AF: 0.122

Gnomad4 SAS AF: 0.0572

Gnomad4 FIN AF: 0.00566

Gnomad4 NFE AF: 0.0111

Gnomad4 OTH AF: 0.0166

Alfa AF: 0.0139 Hom.: 5

Bravo AF: 0.0161

Asia WGS AF: 0.0820 AC: 285 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 09, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.6
DANN	Benign	0.54

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: rs78244765; hg19: chr22-50683658;