dbSNP rs372448915: HIRIP3:p.Arg526Gln (chr16-29993301-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_003609.5(HIRIP3):c.1577G>A(p.Arg526Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000654 in 1,543,306 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000070 ( 0 hom. )

Consequence

HIRIP3
NM_003609.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.83

Publications

1 publications found

Variant links:

Genes affected

HIRIP3 (HGNC:4917): (HIRA interacting protein 3) The HIRA protein shares sequence similarity with Hir1p and Hir2p, the two corepressors of histone gene transcription characterized in the yeast, Saccharomyces cerevisiae. The structural features of the HIRA protein suggest that it may function as part of a multiprotein complex. Several cDNAs encoding HIRA-interacting proteins, or HIRIPs, have been identified. In vitro, the protein encoded by this gene binds HIRA, as well as H2B and H3 core histones, indicating that a complex containing HIRA-HIRIP3 could function in some aspects of chromatin and histone metabolism. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene.[provided by RefSeq, Aug 2011]

HIRIP3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.31559432).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003609.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HIRIP3	NM_003609.5	MANE Select	c.1577G>A	p.Arg526Gln	missense	Exon 7 of 7	NP_003600.2
	HIRIP3	NM_001197323.1		c.*111G>A		3_prime_UTR	Exon 6 of 6	NP_001184252.1	Q9BW71-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HIRIP3	ENST00000279392.8	TSL:1 MANE Select	c.1577G>A	p.Arg526Gln	missense	Exon 7 of 7	ENSP00000279392.3	Q9BW71-1
HIRIP3	ENST00000948389.1		c.1583G>A	p.Arg528Gln	missense	Exon 7 of 7	ENSP00000618448.1
HIRIP3	ENST00000918288.1		c.1568G>A	p.Arg523Gln	missense	Exon 7 of 7	ENSP00000588347.1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000505

AC:

AN:

198034

AF XY:

0.0000667

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000542

Gnomad NFE exome

AF:

0.0000650

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000697

AC:

AN:

1391172

Hom.:

Cov.:

AF XY:

0.0000833

AC XY:

AN XY:

683908

show subpopulations

African (AFR)

AF:

0.0000321

AC:

AN:

31150

American (AMR)

AF:

0.00

AC:

AN:

34880

Ashkenazi Jewish (ASJ)

AF:

0.0000465

AC:

AN:

21526

East Asian (EAS)

AF:

0.000128

AC:

AN:

38940

South Asian (SAS)

AF:

0.0000396

AC:

AN:

75796

European-Finnish (FIN)

AF:

0.0000196

AC:

AN:

51058

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5432

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

1075192

Other (OTH)

AF:

0.000122

AC:

AN:

57198

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152134

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74302

show subpopulations

African (AFR)

AF:

0.0000724

AC:

AN:

41408

American (AMR)

AF:

0.00

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68024

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000340

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000578

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.45

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.012

Eigen

Benign

0.12

Eigen_PC

Benign

0.028

FATHMM_MKL

Benign

0.75

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.023

MetaRNN

Benign

0.32

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

PhyloP100

2.8

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-2.1

REVEL

Benign

0.17

Sift

Benign

0.035

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.38

MVP

0.58

MPC

0.46

ClinPred

0.30

GERP RS

4.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.14

gMVP

0.44

Mutation Taster

=95/5

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over