1-41510751-G-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_024503.5(HIVEP3):c.6921C>A(p.Ser2307Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000198 in 1,581,916 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0012 ( 1 hom., cov: 33)

Exomes 𝑓: 0.000086 ( 0 hom. )

Consequence

HIVEP3
NM_024503.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.73

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 Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0057070553).

BP6

Variant 1-41510751-G-T is Benign according to our data. Variant chr1-41510751-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 3053250.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HIVEP3	NM_024503.5 linkuse as main transcript	c.6921C>A	p.Ser2307Arg	missense_variant	9/9	ENST00000372583.6
HIVEP3	NM_001127714.3 linkuse as main transcript	c.6918C>A	p.Ser2306Arg	missense_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HIVEP3	ENST00000372583.6 linkuse as main transcript	c.6921C>A	p.Ser2307Arg	missense_variant	9/9	1	NM_024503.5	P5	Q5T1R4-1
HIVEP3	ENST00000372584.5 linkuse as main transcript	c.6918C>A	p.Ser2306Arg	missense_variant	8/8	1		A2	Q5T1R4-2
HIVEP3	ENST00000643665.1 linkuse as main transcript	c.6918C>A	p.Ser2306Arg	missense_variant	8/8			A2	Q5T1R4-2
HIVEP3	ENST00000460604.1 linkuse as main transcript	n.1848C>A		non_coding_transcript_exon_variant	5/5	2

Frequencies

GnomAD3 genomes

AF:

0.00122

AC:

186

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00396

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00111

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:

0.00

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.000217

AC:

AN:

202492

Hom.:

AF XY:

0.000126

AC XY:

AN XY:

111232

show subpopulations

Gnomad AFR exome

AF:

0.00318

Gnomad AMR exome

AF:

0.0000972

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000371

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000114

Gnomad OTH exome

AF:

0.000193

GnomAD4 exome

AF:

0.0000860

AC:

123

AN:

1429612

Hom.:

Cov.:

AF XY:

0.0000621

AC XY:

AN XY:

707966

show subpopulations

Gnomad4 AFR exome

AF:

0.00302

Gnomad4 AMR exome

AF:

0.0000721

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000240

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000182

Gnomad4 OTH exome

AF:

0.000271

GnomAD4 genome

AF:

0.00125

AC:

190

AN:

152304

Hom.:

Cov.:

AF XY:

0.00118

AC XY:

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.00404

Gnomad4 AMR

AF:

0.00111

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00236

Alfa

AF:

0.0000676

Hom.:

Bravo

AF:

0.00138

ESP6500AA

AF:

0.00301

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000385

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

HIVEP3-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 13, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.59

Cadd

Benign

Dann

Benign

0.95

Eigen

Benign

-0.79

Eigen_PC

Benign

-0.72

FATHMM_MKL

Benign

0.72

M_CAP

Benign

0.0058

MetaRNN

Benign

0.0057

T;T;T

MetaSVM

Benign

-0.99

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Uncertain

0.51

Polyphen

0.015

B;B;B

Vest4

0.15, 0.12

MutPred

0.20

.;Gain of catalytic residue at S2307 (P = 0.0025);.;

MVP

0.12

MPC

0.21

ClinPred

0.015

GERP RS

2.3

Varity_R

0.086

gMVP

0.13

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