rs144759096

Variant names:

• chr1-41510981-C-A
• rs144759096
• NM_024503.5:c.6691G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-41510981-C-A
• chr1-41510981-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024503.5(HIVEP3):​c.6691G>T​(p.Asp2231Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,178 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D2231N) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: HIVEP3 NM_024503.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.30

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23392716).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HIVEP3	NM_024503.5	c.6691G>T	p.Asp2231Tyr	missense_variant	Exon 9 of 9	ENST00000372583.6	NP_078779.2
HIVEP3	NM_001127714.3	c.6688G>T	p.Asp2230Tyr	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.6691G>T	p.Asp2231Tyr	missense_variant	Exon 9 of 9	1	NM_024503.5	ENSP00000361664.1
HIVEP3	ENST00000372584.5	c.6688G>T	p.Asp2230Tyr	missense_variant	Exon 8 of 8	1		ENSP00000361665.1
HIVEP3	ENST00000643665.1	c.6688G>T	p.Asp2230Tyr	missense_variant	Exon 8 of 8			ENSP00000494598.1
HIVEP3	ENST00000460604.1	n.1618G>T		non_coding_transcript_exon_variant	Exon 5 of 5	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000403 AC: 1 AN: 248344 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 134912

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461178 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 726870

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.0000188

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Benign	-0.078	T
BayesDel_noAF	Benign	-0.25
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	.;T;.
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.81	.;T;T
M_CAP	Benign	0.0099	T
MetaRNN	Benign	0.23	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	.;L;.
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-2.1	.;N;N
REVEL	Benign	0.14
Sift	Pathogenic	0.0	.;D;D
Sift4G	Benign	0.32	.;T;T
Polyphen		0.94	P;P;P
Vest4		0.47, 0.60
MutPred		0.20		.;Gain of phosphorylation at D2231 (P = 0.0465);.;
MVP		0.24
MPC		0.83
ClinPred		0.92	D
GERP RS		5.2
Varity_R		0.32
gMVP		0.38

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs144759096; hg19: chr1-41976652;