22-19385274-G-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_003325.4(HIRA):​c.1329+247C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00417 in 152,296 control chromosomes in the GnomAD database, including 2 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 0.0042 ( 2 hom., cov: 33)

Consequence

HIRA
NM_003325.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.870
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)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.87).
BS2
High AC in GnomAd4 at 635 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
HIRANM_003325.4 linkuse as main transcriptc.1329+247C>T intron_variant ENST00000263208.5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
HIRAENST00000263208.5 linkuse as main transcriptc.1329+247C>T intron_variant 1 NM_003325.4 P1P54198-1
HIRAENST00000340170.8 linkuse as main transcriptc.1329+247C>T intron_variant 1 P54198-2
C22orf39ENST00000509549.5 linkuse as main transcriptc.*1205+247C>T intron_variant, NMD_transcript_variant 2

Frequencies

GnomAD3 genomes
AF:
0.00417
AC:
635
AN:
152178
Hom.:
2
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000772
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0158
Gnomad ASJ
AF:
0.0116
Gnomad EAS
AF:
0.000385
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00367
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00392
Gnomad OTH
AF:
0.00622
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.00417
AC:
635
AN:
152296
Hom.:
2
Cov.:
33
AF XY:
0.00414
AC XY:
308
AN XY:
74458
show subpopulations
Gnomad4 AFR
AF:
0.000770
Gnomad4 AMR
AF:
0.0158
Gnomad4 ASJ
AF:
0.0116
Gnomad4 EAS
AF:
0.000386
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00367
Gnomad4 NFE
AF:
0.00392
Gnomad4 OTH
AF:
0.00616
Alfa
AF:
0.00426
Hom.:
0
Bravo
AF:
0.00587

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.87
CADD
Benign
5.8
DANN
Benign
0.63

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.

Other links and lift over

dbSNP: rs1008246; hg19: chr22-19372797; API