NM_199321.3:c.19C>G

Variant names:

• chr17-39868373-C-G
• rs11557466
• NM_199321.3:c.19C>G

Variant summary

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

The NM_199321.3(ZPBP2):​c.19C>G​(p.Leu7Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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.

• Frequency: Genomes: not found (cov: 31)
• Consequence: ZPBP2 NM_199321.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.16
• Publications: 48 publications found

Genes affected

ZPBP2 (HGNC:20678): (zona pellucida binding protein 2) Predicted to be involved in acrosome assembly and binding activity of sperm to zona pellucida. Predicted to act upstream of or within membrane lipid metabolic process and regulation of gene expression. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000302760 (HGNC:):

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=0.21296388).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZPBP2	NM_199321.3	c.19C>G	p.Leu7Val	missense_variant	Exon 1 of 8	ENST00000348931.9	NP_955353.1
ZPBP2	NM_198844.3	c.19C>G	p.Leu7Val	missense_variant	Exon 1 of 7		NP_942141.2
ZPBP2	XM_047435318.1	c.19C>G	p.Leu7Val	missense_variant	Exon 1 of 7		XP_047291274.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZPBP2	ENST00000348931.9	c.19C>G	p.Leu7Val	missense_variant	Exon 1 of 8	1	NM_199321.3	ENSP00000335384.5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 62

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.078	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	21
DANN	Benign	0.57
DEOGEN2	Benign	0.062	T;.;T;.
Eigen	Benign	0.070
Eigen_PC	Benign	-0.073
FATHMM_MKL	Benign	0.57	D
LIST_S2	Benign	0.79	T;T;T;T
M_CAP	Benign	0.062	D
MetaRNN	Benign	0.21	T;T;T;T
MetaSVM	Benign	-0.65	T
MutationAssessor	Benign	1.9	L;.;.;L
PhyloP100		1.2
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.1	N;.;.;N
REVEL	Benign	0.075
Sift	Benign	0.11	T;.;.;D
Sift4G	Pathogenic	0.0	D;D;D;D
Polyphen		1.0	D;.;.;D
Vest4		0.47
MutPred		0.31		Gain of catalytic residue at L7 (P = 0.0064);Gain of catalytic residue at L7 (P = 0.0064);Gain of catalytic residue at L7 (P = 0.0064);Gain of catalytic residue at L7 (P = 0.0064);
MVP		0.20
MPC		0.63
ClinPred		0.66	D
GERP RS		2.0
PromoterAI		0.13	Neutral
Varity_R		0.067
gMVP		0.25

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: rs11557466; hg19: chr17-38024626;