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GeneBe

22-19354025-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_003325.4(HIRA):c.2655G>A(p.Pro885=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000365 in 1,613,320 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00090 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00031 ( 0 hom. )

Consequence

HIRA
NM_003325.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.35
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]
C22orf39 (HGNC:27012): (chromosome 22 open reading frame 39)

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.58).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 22-19354025-C-T is Benign according to our data. Variant chr22-19354025-C-T is described in ClinVar as [Benign]. Clinvar id is 713436.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-2.35 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 137 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
HIRANM_003325.4 linkuse as main transcriptc.2655G>A p.Pro885= synonymous_variant 22/25 ENST00000263208.5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
HIRAENST00000263208.5 linkuse as main transcriptc.2655G>A p.Pro885= synonymous_variant 22/251 NM_003325.4 P1P54198-1
HIRAENST00000340170.8 linkuse as main transcriptc.2034G>A p.Pro678= synonymous_variant 18/211 P54198-2
C22orf39ENST00000509549.5 linkuse as main transcriptc.*2425G>A 3_prime_UTR_variant, NMD_transcript_variant 22/242

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000900
AC:
137
AN:
152176
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00220
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000917
Gnomad ASJ
AF:
0.00576
Gnomad EAS
AF:
0.000385
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000132
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.000530
AC:
132
AN:
249038
Hom.:
0
AF XY:
0.000423
AC XY:
57
AN XY:
134688
show subpopulations
Gnomad AFR exome
AF:
0.00239
Gnomad AMR exome
AF:
0.000669
Gnomad ASJ exome
AF:
0.00490
Gnomad EAS exome
AF:
0.000109
Gnomad SAS exome
AF:
0.0000330
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000142
Gnomad OTH exome
AF:
0.000493
GnomAD4 exome
AF:
0.000309
AC:
452
AN:
1461026
Hom.:
0
Cov.:
31
AF XY:
0.000305
AC XY:
222
AN XY:
726698
show subpopulations
Gnomad4 AFR exome
AF:
0.00302
Gnomad4 AMR exome
AF:
0.000717
Gnomad4 ASJ exome
AF:
0.00571
Gnomad4 EAS exome
AF:
0.0000756
Gnomad4 SAS exome
AF:
0.0000465
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000108
Gnomad4 OTH exome
AF:
0.000596
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000900
AC:
137
AN:
152294
Hom.:
0
Cov.:
32
AF XY:
0.000806
AC XY:
60
AN XY:
74478
show subpopulations
Gnomad4 AFR
AF:
0.00219
Gnomad4 AMR
AF:
0.000916
Gnomad4 ASJ
AF:
0.00576
Gnomad4 EAS
AF:
0.000386
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000132
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.000648
Hom.:
0
Bravo
AF:
0.00102
Asia WGS
AF:
0.000577
AC:
2
AN:
3478
EpiCase
AF:
0.000436
EpiControl
AF:
0.000534

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.58
Cadd
Benign
7.6
Dann
Benign
0.94
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.8

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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.

Other links and lift over

dbSNP: rs146643449; hg19: chr22-19341548; COSMIC: COSV99600467; API