rs72669005

Positions:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000372583.6(HIVEP3):c.7126C>T(p.Pro2376Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0559 in 1,576,608 control chromosomes in the GnomAD database, including 3,656 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.086 ( 913 hom., cov: 33)

Exomes 𝑓: 0.053 ( 2743 hom. )

Consequence

HIVEP3
ENST00000372583.6 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.17

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0012972653).

BP6

Variant 1-41510546-G-A is Benign according to our data. Variant chr1-41510546-G-A is described in ClinVar as [Benign]. Clinvar id is 402940.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HIVEP3	NM_024503.5 linkuse as main transcript	c.7126C>T	p.Pro2376Ser	missense_variant	9/9	ENST00000372583.6	NP_078779.2
HIVEP3	NM_001127714.3 linkuse as main transcript	c.7123C>T	p.Pro2375Ser	missense_variant	8/8		NP_001121186.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HIVEP3	ENST00000372583.6 linkuse as main transcript	c.7126C>T	p.Pro2376Ser	missense_variant	9/9	1	NM_024503.5	ENSP00000361664	P5	Q5T1R4-1
HIVEP3	ENST00000372584.5 linkuse as main transcript	c.7123C>T	p.Pro2375Ser	missense_variant	8/8	1		ENSP00000361665	A2	Q5T1R4-2
HIVEP3	ENST00000643665.1 linkuse as main transcript	c.7123C>T	p.Pro2375Ser	missense_variant	8/8			ENSP00000494598	A2	Q5T1R4-2
HIVEP3	ENST00000460604.1 linkuse as main transcript	n.2053C>T		non_coding_transcript_exon_variant	5/5	2

Frequencies

GnomAD3 genomes

AF:

0.0859

AC:

13063

AN:

152078

Hom.:

907

Cov.:

show subpopulations

Gnomad AFR

AF:

0.187

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.0584

Gnomad ASJ

AF:

0.0522

Gnomad EAS

AF:

0.00251

Gnomad SAS

AF:

0.115

Gnomad FIN

AF:

0.0369

Gnomad MID

AF:

0.111

Gnomad NFE

AF:

0.0452

Gnomad OTH

AF:

0.0766

GnomAD3 exomes

AF:

0.0659

AC:

12199

AN:

185134

Hom.:

604

AF XY:

0.0671

AC XY:

6630

AN XY:

98832

show subpopulations

Gnomad AFR exome

AF:

0.201

Gnomad AMR exome

AF:

0.0659

Gnomad ASJ exome

AF:

0.0557

Gnomad EAS exome

AF:

0.00310

Gnomad SAS exome

AF:

0.119

Gnomad FIN exome

AF:

0.0356

Gnomad NFE exome

AF:

0.0489

Gnomad OTH exome

AF:

0.0589

GnomAD4 exome

AF:

0.0527

AC:

75009

AN:

1424412

Hom.:

2743

Cov.:

AF XY:

0.0539

AC XY:

38023

AN XY:

704980

show subpopulations

Gnomad4 AFR exome

AF:

0.197

Gnomad4 AMR exome

AF:

0.0641

Gnomad4 ASJ exome

AF:

0.0559

Gnomad4 EAS exome

AF:

0.00365

Gnomad4 SAS exome

AF:

0.114

Gnomad4 FIN exome

AF:

0.0366

Gnomad4 NFE exome

AF:

0.0450

Gnomad4 OTH exome

AF:

0.0612

GnomAD4 genome

AF:

0.0861

AC:

13100

AN:

152196

Hom.:

913

Cov.:

AF XY:

0.0851

AC XY:

6332

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.188

Gnomad4 AMR

AF:

0.0582

Gnomad4 ASJ

AF:

0.0522

Gnomad4 EAS

AF:

0.00252

Gnomad4 SAS

AF:

0.114

Gnomad4 FIN

AF:

0.0369

Gnomad4 NFE

AF:

0.0452

Gnomad4 OTH

AF:

0.0777

Alfa

AF:

0.0516

Hom.:

177

Bravo

AF:

0.0916

TwinsUK

AF:

0.0361

AC:

134

ALSPAC

AF:

0.0480

AC:

185

ESP6500AA

AF:

0.180

AC:

790

ESP6500EA

AF:

0.0496

AC:

426

ExAC

AF:

0.0574

AC:

6830

Asia WGS

AF:

0.0870

AC:

304

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

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

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: MAF -

HIVEP3-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 05, 2024

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

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.63

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.12

.;T;.

Eigen

Benign

0.044

Eigen_PC

Benign

0.11

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.80

.;T;T

MetaRNN

Benign

0.0013

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.1

.;L;.

MutationTaster

Benign

0.66

N;N;N;N

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-1.1

.;N;N

REVEL

Benign

0.027

Sift

Benign

0.050

.;D;T

Sift4G

Benign

0.077

.;T;T

Polyphen

0.87

P;P;P

Vest4

0.073, 0.13

MPC

0.30

ClinPred

0.012

GERP RS

4.3

Varity_R

0.092

gMVP

0.085

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over