1-41510659-G-C

Variant names:

• chr1-41510659-G-C
• rs58930436
• NM_024503.5:c.7013C>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_024503.5(HIVEP3):​c.7013C>G​(p.Pro2338Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000017 in 1,527,004 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict 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. P2338L) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: HIVEP3 NM_024503.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.188
• Publications: 3 publications found

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]

ENSG00000295052 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.043417096).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024503.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HIVEP3	NM_024503.5	MANE Select	c.7013C>G	p.Pro2338Arg	missense	Exon 9 of 9	NP_078779.2	Q5T1R4-1
	HIVEP3	NM_001127714.3		c.7010C>G	p.Pro2337Arg	missense	Exon 8 of 8	NP_001121186.1	Q5T1R4-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HIVEP3	ENST00000372583.6	TSL:1 MANE Select	c.7013C>G	p.Pro2338Arg	missense	Exon 9 of 9	ENSP00000361664.1	Q5T1R4-1
	HIVEP3	ENST00000372584.5	TSL:1	c.7010C>G	p.Pro2337Arg	missense	Exon 8 of 8	ENSP00000361665.1	Q5T1R4-2
	HIVEP3	ENST00000643665.1		c.7010C>G	p.Pro2337Arg	missense	Exon 8 of 8	ENSP00000494598.1	Q5T1R4-2

Frequencies

GnomAD3 genomes AF: 0.0000591 AC: 9 AN: 152172 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000519 AC: 7 AN: 135002 AF XY: 0.0000276

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000458

Gnomad FIN exome AF: 0.0000876

Gnomad NFE exome AF: 0.0000199

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000124 AC: 17 AN: 1374714 Hom.: 0 Cov.: 34 AF XY: 0.0000104 AC XY: 7 AN XY: 675406

African (AFR) AF: 0.0000641 AC: 2 AN: 31194

American (AMR) AF: 0.00 AC: 0 AN: 34374

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24118

East Asian (EAS) AF: 0.000169 AC: 6 AN: 35498

South Asian (SAS) AF: 0.00 AC: 0 AN: 77438

European-Finnish (FIN) AF: 0.000163 AC: 7 AN: 42936

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4702

European-Non Finnish (NFE) AF: 0.00000187 AC: 2 AN: 1067572

Other (OTH) AF: 0.00 AC: 0 AN: 56882

GnomAD4 genome AF: 0.0000591 AC: 9 AN: 152290 Hom.: 0 Cov.: 33 AF XY: 0.0000537 AC XY: 4 AN XY: 74478

African (AFR) AF: 0.0000722 AC: 3 AN: 41552

American (AMR) AF: 0.00 AC: 0 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.000188 AC: 2 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68000

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.0000258 Hom.: 6

Bravo AF: 0.0000113

ExAC AF: 0.0000288 AC: 3

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.35
DANN	Benign	0.32
DEOGEN2	Benign	0.069	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.043	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.19
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.38	N
REVEL	Benign	0.020
Sift	Benign	0.35	T
Sift4G	Benign	0.79	T
Polyphen		0.0010	B
Vest4		0.060
MutPred		0.29		Gain of methylation at P2338 (P = 0.0159)
MVP		0.055
MPC		0.21
ClinPred		0.025	T
GERP RS		-5.5
Varity_R		0.030
gMVP		0.042
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs58930436; hg19: chr1-41976330;