Variant 1-41510860-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_024503.5(HIVEP3):c.6812G>A(p.Gly2271Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000958 in 1,461,058 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

HIVEP3
NM_024503.5 missense

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 0.361

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03235492).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HIVEP3	NM_024503.5 link	c.6812G>A	p.Gly2271Asp	missense_variant	9/9	ENST00000372583.6	NP_078779.2	Q5T1R4-1
HIVEP3	NM_001127714.3 link	c.6809G>A	p.Gly2270Asp	missense_variant	8/8		NP_001121186.1	Q5T1R4-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
HIVEP3	ENST00000372583.6 link	c.6812G>A	p.Gly2271Asp	missense_variant	9/9	1	NM_024503.5	ENSP00000361664.1	Q5T1R4-1
HIVEP3	ENST00000372584.5 link	c.6809G>A	p.Gly2270Asp	missense_variant	8/8	1		ENSP00000361665.1	Q5T1R4-2
HIVEP3	ENST00000643665.1 link	c.6809G>A	p.Gly2270Asp	missense_variant	8/8			ENSP00000494598.1	Q5T1R4-2
HIVEP3	ENST00000460604.1 link	n.1739G>A		non_coding_transcript_exon_variant	5/5	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000958

AC:

AN:

1461058

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726822

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000117

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000468

Hom.:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

HIVEP3-related disorder

Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 08, 2024

The HIVEP3 c.6812G>A variant is predicted to result in the amino acid substitution p.Gly2271Asp. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.69

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.047

.;T;.

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.55

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.58

.;T;T

M_CAP

Benign

0.0029

MetaRNN

Benign

0.032

T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.90

.;L;.

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-0.26

.;N;N

REVEL

Benign

0.092

Sift

Uncertain

0.0040

.;D;D

Sift4G

Benign

0.077

.;T;T

Polyphen

0.0010

B;B;B

Vest4

0.072, 0.066

MutPred

0.033

.;Loss of glycosylation at K2276 (P = 0.189);.;

MVP

0.14

MPC

0.24

ClinPred

0.26

GERP RS

1.9

Varity_R

0.081

gMVP

0.077

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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