Variant chr22-19356246-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_003325.4(HIRA):c.2439A>G(p.Leu813=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000604 in 1,614,056 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0035 ( 3 hom., cov: 32)

Exomes 𝑓: 0.00031 ( 2 hom. )

Consequence

HIRA
NM_003325.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.0800

Variant links:

Genes affected

HIRA (HGNC:4916): (histone cell cycle regulator) This gene encodes a histone chaperone that preferentially places the variant histone H3.3 in nucleosomes. Orthologs of this gene in yeast, flies, and plants are necessary for the formation of transcriptionally silent heterochomatin. This gene plays an important role in the formation of the senescence-associated heterochromatin foci. These foci likely mediate the irreversible cell cycle changes that occur in senescent cells. It is considered the primary candidate gene in some haploinsufficiency syndromes such as DiGeorge syndrome, and insufficient production of the gene may disrupt normal embryonic development. [provided by RefSeq, Jul 2008]

HIRA links:

C22orf39 (HGNC:27012): (chromosome 22 open reading frame 39)

C22orf39 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP6

Variant 22-19356246-T-C is Benign according to our data. Variant chr22-19356246-T-C is described in ClinVar as [Benign]. Clinvar id is 727503.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.08 with no splicing effect.

BS2

High AC in GnomAd4 at 526 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HIRA	NM_003325.4 linkuse as main transcript	c.2439A>G	p.Leu813=	synonymous_variant	20/25	ENST00000263208.5	NP_003316.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HIRA	ENST00000263208.5 linkuse as main transcript	c.2439A>G	p.Leu813=	synonymous_variant	20/25	1	NM_003325.4	ENSP00000263208	P1	P54198-1
HIRA	ENST00000340170.8 linkuse as main transcript	c.1818A>G	p.Leu606=	synonymous_variant	16/21	1		ENSP00000345350		P54198-2
C22orf39	ENST00000509549.5 linkuse as main transcript	c.*2315A>G		3_prime_UTR_variant, NMD_transcript_variant	21/24	2		ENSP00000424903

Frequencies

GnomAD3 genomes

AF:

0.00345

AC:

525

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0118

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00177

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.000847

AC:

213

AN:

251436

Hom.:

AF XY:

0.000611

AC XY:

AN XY:

135894

show subpopulations

Gnomad AFR exome

AF:

0.0111

Gnomad AMR exome

AF:

0.000868

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000307

AC:

449

AN:

1461788

Hom.:

Cov.:

AF XY:

0.000257

AC XY:

187

AN XY:

727214

show subpopulations

Gnomad4 AFR exome

AF:

0.0114

Gnomad4 AMR exome

AF:

0.000827

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.000364

GnomAD4 genome

AF:

0.00345

AC:

526

AN:

152268

Hom.:

Cov.:

AF XY:

0.00349

AC XY:

260

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.0118

Gnomad4 AMR

AF:

0.00176

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00176

Hom.:

Bravo

AF:

0.00383

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 13, 2018	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Apr 01, 2024	HIRA: BP4, BP7, BS1, BS2 -

HIRA-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 11, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

5.0

DANN

Benign

0.91

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over