NM_024503.5:c.7015A>G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_024503.5(HIVEP3):c.7015A>G(p.Thr2339Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.994 in 1,533,770 control chromosomes in the GnomAD database, including 757,851 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.97 ( 71866 hom., cov: 32)

Exomes 𝑓: 1.0 ( 685985 hom. )

Consequence

HIVEP3
NM_024503.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.588

Publications

19 publications found

Variant links:

Genes affected

HIVEP3 (HGNC:13561): (HIVEP zinc finger 3) This gene encodes a member of the human immunodeficiency virus type 1 enhancer-binding protein family. Members of this protein family contain multiple zinc finger and acid-rich (ZAS) domains and serine-threonine rich regions. This protein acts as a transcription factor and is able to regulate nuclear factor kappaB-mediated transcription by binding the kappaB motif in target genes. This protein also binds the recombination signal sequence that flanks the V, D, and J regions of immunoglobulin and T-cell receptors. Alternate splicing results in both coding and non-coding transcript variants. [provided by RefSeq, Sep 2011]

HIVEP3 links:

ENSG00000295052 (HGNC:):

ENSG00000295052 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.3137944E-6).

BP6

Variant 1-41510657-T-C is Benign according to our data. Variant chr1-41510657-T-C is described in ClinVar as Benign. ClinVar VariationId is 402941.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.992 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HIVEP3	NM_024503.5 link	c.7015A>G	p.Thr2339Ala	missense_variant	Exon 9 of 9	ENST00000372583.6	NP_078779.2	Q5T1R4-1
HIVEP3	NM_001127714.3 link	c.7012A>G	p.Thr2338Ala	missense_variant	Exon 8 of 8		NP_001121186.1	Q5T1R4-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HIVEP3	ENST00000372583.6 link	c.7015A>G	p.Thr2339Ala	missense_variant	Exon 9 of 9	1	NM_024503.5	ENSP00000361664.1		Q5T1R4-1

Frequencies

GnomAD3 genomes

AF:

0.971

AC:

147672

AN:

152118

Hom.:

71818

Cov.:

show subpopulations

Gnomad AFR

AF:

0.901

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.988

Gnomad ASJ

AF:

1.00

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.999

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

0.991

Gnomad NFE

AF:

0.999

Gnomad OTH

AF:

0.978

GnomAD2 exomes

AF:

0.993

AC:

139881

AN:

140928

AF XY:

0.994

show subpopulations

Gnomad AFR exome

AF:

0.890

Gnomad AMR exome

AF:

0.994

Gnomad ASJ exome

AF:

1.00

Gnomad EAS exome

AF:

1.00

Gnomad FIN exome

AF:

1.00

Gnomad NFE exome

AF:

0.999

Gnomad OTH exome

AF:

0.993

GnomAD4 exome

AF:

0.996

AC:

1376544

AN:

1381534

Hom.:

685985

Cov.:

AF XY:

0.997

AC XY:

677562

AN XY:

679732

show subpopulations

African (AFR)

AF:

0.892

AC:

27965

AN:

31354

American (AMR)

AF:

0.993

AC:

34802

AN:

35040

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

24507

AN:

24510

East Asian (EAS)

AF:

1.00

AC:

35566

AN:

35566

South Asian (SAS)

AF:

1.00

AC:

78167

AN:

78180

European-Finnish (FIN)

AF:

1.00

AC:

43817

AN:

43820

Middle Eastern (MID)

AF:

0.987

AC:

4589

AN:

4650

European-Non Finnish (NFE)

AF:

0.999

AC:

1070471

AN:

1071254

Other (OTH)

AF:

0.991

AC:

56660

AN:

57160

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

295

590

885

1180

1475

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21270

42540

63810

85080

106350

<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:

0.971

AC:

147778

AN:

152236

Hom.:

71866

Cov.:

AF XY:

0.972

AC XY:

72340

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.901

AC:

37404

AN:

41528

American (AMR)

AF:

0.988

AC:

15120

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

3469

AN:

3470

East Asian (EAS)

AF:

1.00

AC:

5158

AN:

5158

South Asian (SAS)

AF:

0.999

AC:

4813

AN:

4816

European-Finnish (FIN)

AF:

1.00

AC:

10626

AN:

10626

Middle Eastern (MID)

AF:

0.990

AC:

291

AN:

294

European-Non Finnish (NFE)

AF:

0.999

AC:

67919

AN:

68018

Other (OTH)

AF:

0.978

AC:

2066

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

219

438

658

877

1096

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

914

1828

2742

3656

4570

<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:

0.987

Hom.:

13008

Bravo

AF:

0.967

TwinsUK

AF:

0.999

AC:

3705

ALSPAC

AF:

0.999

AC:

3849

ESP6500AA

AF:

0.915

AC:

3684

ESP6500EA

AF:

0.997

AC:

7782

ExAC

AF:

0.981

AC:

87682

Asia WGS

AF:

0.991

AC:

3446

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

HIVEP3-related disorder

Benign:1

Apr 30, 2021

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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). -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.051

BayesDel_addAF

Benign

-0.83

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.22

(source)

DANN

Benign

0.13

DEOGEN2

Benign

0.053

.;T;.

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0034

LIST_S2

Benign

0.18

.;T;T

MetaRNN

Benign

0.0000013

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-0.63

.;N;.

PhyloP100

0.59

PrimateAI

Benign

0.40

PROVEAN

Benign

0.17

.;N;N

REVEL

Benign

0.042

Sift

Benign

1.0

.;T;T

Sift4G

Benign

1.0

.;T;T

Polyphen

0.0

B;B;B

Vest4

0.022, 0.015

MPC

0.18

ClinPred

0.00068

GERP RS

2.2

Varity_R

0.027

gMVP

0.043

Mutation Taster

=100/0

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over