rs2810565

Variant names:

• chr1-41581141-C-G
• rs2810565
• NM_024503.5:c.3657G>C

Your query was ambiguous. Multiple possible variants found:

• chr1-41581141-C-G
• chr1-41581141-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024503.5(HIVEP3):​c.3657G>C​(p.Gln1219His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 151,916 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. Q1219Q) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 29)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HIVEP3 NM_024503.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.387
• Publications: 11 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09711605).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HIVEP3	NM_024503.5	c.3657G>C	p.Gln1219His	missense_variant	Exon 4 of 9	ENST00000372583.6	NP_078779.2
HIVEP3	NM_001127714.3	c.3657G>C	p.Gln1219His	missense_variant	Exon 3 of 8		NP_001121186.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HIVEP3	ENST00000372583.6	c.3657G>C	p.Gln1219His	missense_variant	Exon 4 of 9	1	NM_024503.5	ENSP00000361664.1
HIVEP3	ENST00000372584.5	c.3657G>C	p.Gln1219His	missense_variant	Exon 3 of 8	1		ENSP00000361665.1
HIVEP3	ENST00000643665.1	c.3657G>C	p.Gln1219His	missense_variant	Exon 3 of 8			ENSP00000494598.1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151916 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1396136 Hom.: 0 Cov.: 68 AF XY: 0.00 AC XY: 0 AN XY: 686450

African (AFR) AF: 0.00 AC: 0 AN: 31740

American (AMR) AF: 0.00 AC: 0 AN: 37014

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21574

East Asian (EAS) AF: 0.00 AC: 0 AN: 39096

South Asian (SAS) AF: 0.00 AC: 0 AN: 74926

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50296

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5426

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078506

Other (OTH) AF: 0.00 AC: 0 AN: 57558

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 151916 Hom.: 0 Cov.: 29 AF XY: 0.0000135 AC XY: 1 AN XY: 74208

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 41296

American (AMR) AF: 0.00 AC: 0 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4804

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67992

Other (OTH) AF: 0.00 AC: 0 AN: 2084

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 21666

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	6.7
DANN	Benign	0.72
DEOGEN2	Benign	0.079	.;T;.
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.56
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.56	.;T;T
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.097	T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.1	M;M;M
PhyloP100		0.39
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.24	.;N;N
REVEL	Benign	0.035
Sift	Benign	0.10	.;T;T
Sift4G	Benign	0.35	.;T;T
Polyphen		0.35	B;B;B
Vest4		0.25, 0.26
MutPred		0.080		Loss of glycosylation at P1221 (P = 0.1688);Loss of glycosylation at P1221 (P = 0.1688);Loss of glycosylation at P1221 (P = 0.1688);
MVP		0.14
MPC		0.53
ClinPred		0.12	T
GERP RS		3.0
Varity_R		0.052
gMVP		0.47
Mutation Taster		=96/4	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: rs2810565; hg19: chr1-42046812;