rs1644443460

Variant names:

• chr1-41510860-C-T
• rs1644443460
• NM_024503.5:c.6812G>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_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
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 0.361

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]

ACMG classification

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 rank	MANE	Protein	UniProt
HIVEP3	NM_024503.5	c.6812G>A	p.Gly2271Asp	missense_variant	Exon 9 of 9	ENST00000372583.6	NP_078779.2
HIVEP3	NM_001127714.3	c.6809G>A	p.Gly2270Asp	missense_variant	Exon 8 of 8		NP_001121186.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HIVEP3	ENST00000372583.6	c.6812G>A	p.Gly2271Asp	missense_variant	Exon 9 of 9	1	NM_024503.5	ENSP00000361664.1
HIVEP3	ENST00000372584.5	c.6809G>A	p.Gly2270Asp	missense_variant	Exon 8 of 8	1		ENSP00000361665.1
HIVEP3	ENST00000643665.1	c.6809G>A	p.Gly2270Asp	missense_variant	Exon 8 of 8			ENSP00000494598.1
HIVEP3	ENST00000460604.1	n.1739G>A		non_coding_transcript_exon_variant	Exon 5 of 5	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000958 AC: 14 AN: 1461058 Hom.: 0 Cov.: 34 AF XY: 0.00000275 AC XY: 2 AN XY: 726822

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.: 32

Alfa AF: 0.0000468 Hom.: 0

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

HIVEP3-related disorder Uncertain:1

Apr 08, 2024

PreventionGenetics, part of Exact Sciences

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: clinical testing

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	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Benign	0.047	.;T;.
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.55
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.58	.;T;T
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.032	T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.90	.;L;.
PrimateAI	Uncertain	0.53	T
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	T
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

Other links and lift over

dbSNP: rs1644443460; hg19: chr1-41976531;