Genetic Variant NM_003609.5:c.1631A>T (chr16-29993247-T-A) – 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.1631A>T(p.His544Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000697 in 1,435,328 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H544R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

HIRIP3
NM_003609.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.48

Publications

0 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=0.4145927).

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.1631A>T	p.His544Leu	missense	Exon 7 of 7	NP_003600.2
	HIRIP3	NM_001197323.1		c.*165A>T		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.1631A>T	p.His544Leu	missense	Exon 7 of 7	ENSP00000279392.3	Q9BW71-1
HIRIP3	ENST00000948389.1		c.1637A>T	p.His546Leu	missense	Exon 7 of 7	ENSP00000618448.1
HIRIP3	ENST00000918288.1		c.1622A>T	p.His541Leu	missense	Exon 7 of 7	ENSP00000588347.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.97e-7

AC:

AN:

1435328

Hom.:

Cov.:

AF XY:

0.00000140

AC XY:

AN XY:

711820

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32466

American (AMR)

AF:

0.00

AC:

AN:

40584

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24474

East Asian (EAS)

AF:

0.0000254

AC:

AN:

39402

South Asian (SAS)

AF:

0.00

AC:

AN:

82420

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52642

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5650

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1098462

Other (OTH)

AF:

0.00

AC:

AN:

59228

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.42

BayesDel_addAF

Benign

-0.031

BayesDel_noAF

Benign

-0.28

CADD

Uncertain

(source)

DANN

Uncertain

0.97

DEOGEN2

Benign

0.12

Eigen

Uncertain

0.35

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Benign

0.51

LIST_S2

Benign

0.67

M_CAP

Benign

0.021

MetaRNN

Benign

0.41

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

PhyloP100

1.5

PrimateAI

Uncertain

0.62

PROVEAN

Pathogenic

-5.7

REVEL

Benign

0.18

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0060

Polyphen

1.0

Vest4

0.50

MutPred

0.21

Loss of sheet (P = 0.0457)

MVP

0.66

MPC

0.33

ClinPred

0.96

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.63

gMVP

0.39

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over