1-41583361-G-C

Position:

• chr1-41583361-G-C

Variant summary

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

The NM_024503.5(HIVEP3):​c.1437C>G​(p.Ser479Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,460,588 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S479S) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: HIVEP3 NM_024503.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.366

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HIVEP3	NM_024503.5	c.1437C>G	p.Ser479Arg	missense_variant	4/9	ENST00000372583.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HIVEP3	ENST00000372583.6	c.1437C>G	p.Ser479Arg	missense_variant	4/9	1	NM_024503.5	P5
HIVEP3	ENST00000372584.5	c.1437C>G	p.Ser479Arg	missense_variant	3/8	1		A2
HIVEP3	ENST00000643665.1	c.1437C>G	p.Ser479Arg	missense_variant	3/8			A2

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1460588 Hom.: 0 Cov.: 67 AF XY: 0.00000138 AC XY: 1 AN XY: 726442

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000360

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Benign	0.0092	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	17
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	.;T;.
Eigen	Benign	-0.075
Eigen_PC	Benign	-0.18
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.83	.;T;T
M_CAP	Benign	0.031	D
MetaRNN	Uncertain	0.58	D;D;D
MetaSVM	Benign	-0.83	T
MutationAssessor	Uncertain	2.5	M;M;M
MutationTaster	Benign	0.0045	P;P;P;P
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-1.2	.;N;N
REVEL	Benign	0.24
Sift	Uncertain	0.028	.;D;D
Sift4G	Uncertain	0.0030	.;D;D
Polyphen		1.0	D;D;D
Vest4		0.63, 0.64
MutPred		0.15		Gain of MoRF binding (P = 0.0289);Gain of MoRF binding (P = 0.0289);Gain of MoRF binding (P = 0.0289);
MVP		0.49
MPC		0.79
ClinPred		0.94	D
GERP RS		0.18
Varity_R		0.15
gMVP		0.69

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

Other links and lift over

dbSNP: rs2984694; hg19: chr1-42049032;