chr22-50245269-G-T

Position:

• chr22-50245269-G-T

Variant summary

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

The NM_032019.6(HDAC10):​c.*238C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00137 in 597,482 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0040 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00049 (0 hom.)
• Consequence: HDAC10 NM_032019.6 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.144

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 Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 22-50245269-G-T is Benign according to our data. Variant chr22-50245269-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 1187059.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HDAC10	NM_032019.6	c.*238C>A		3_prime_UTR_variant	20/20	ENST00000216271.10
HDAC10	NM_001159286.2	c.*238C>A		3_prime_UTR_variant	19/19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HDAC10	ENST00000216271.10	c.*238C>A		3_prime_UTR_variant	20/20	1	NM_032019.6	P1
	ENST00000685176.2	n.633G>T		non_coding_transcript_exon_variant	1/1
HDAC10	ENST00000415993.5	c.*1769C>A		3_prime_UTR_variant, NMD_transcript_variant	18/18	1
HDAC10	ENST00000626012.2	c.*1860C>A		3_prime_UTR_variant	19/19	5

Frequencies

GnomAD3 genomes AF: 0.00396 AC: 596 AN: 150622 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.0139

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00120

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: 0.0000296

Gnomad OTH AF: 0.00338

GnomAD4 exome AF: 0.000495 AC: 221 AN: 446750 Hom.: 0 Cov.: 0 AF XY: 0.000427 AC XY: 101 AN XY: 236740

Gnomad4 AFR exome AF: 0.0133

Gnomad4 AMR exome AF: 0.000892

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000643

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000373

Gnomad4 OTH exome AF: 0.00120

GnomAD4 genome AF: 0.00396 AC: 597 AN: 150732 Hom.: 1 Cov.: 32 AF XY: 0.00376 AC XY: 277 AN XY: 73598

Gnomad4 AFR AF: 0.0139

Gnomad4 AMR AF: 0.00120

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000296

Gnomad4 OTH AF: 0.00335

Alfa AF: 0.00312 Hom.: 1

Bravo AF: 0.00478

Asia WGS AF: 0.000867 AC: 3 AN: 3476

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 17, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.1
DANN	Benign	0.83

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: rs191771005; hg19: chr22-50683698;