17-39871571-G-A

Position:

• chr17-39871571-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_199321.3(ZPBP2):​c.352G>A​(p.Ala118Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00488 in 1,600,030 control chromosomes in the GnomAD database, including 362 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.027 (196 hom., cov: 32)
  • Exomes 𝑓: 0.0026 (166 hom.)
• Consequence: ZPBP2 NM_199321.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 3.04

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0013778508).
• BP6: Variant 17-39871571-G-A is Benign according to our data. Variant chr17-39871571-G-A is described in ClinVar as [Benign]. Clinvar id is 781282.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0918 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZPBP2	NM_199321.3	c.352G>A	p.Ala118Thr	missense_variant	4/8	ENST00000348931.9	NP_955353.1
ZPBP2	NM_198844.3	c.286G>A	p.Ala96Thr	missense_variant	3/7		NP_942141.2
ZPBP2	XM_047435318.1	c.352G>A	p.Ala118Thr	missense_variant	4/7		XP_047291274.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZPBP2	ENST00000348931.9	c.352G>A	p.Ala118Thr	missense_variant	4/8	1	NM_199321.3	ENSP00000335384	P1
ZPBP2	ENST00000377940.3	c.286G>A	p.Ala96Thr	missense_variant	3/7	1		ENSP00000367174
ZPBP2	ENST00000584588.5	c.352G>A	p.Ala118Thr	missense_variant	4/7	5		ENSP00000462067
ZPBP2	ENST00000583811.5	c.53-699G>A		intron_variant		3		ENSP00000462463

Frequencies

GnomAD3 genomes AF: 0.0269 AC: 4084 AN: 152072 Hom.: 192 Cov.: 32

Gnomad AFR AF: 0.0941

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00838

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.0192

GnomAD3 exomes AF: 0.00679 AC: 1630 AN: 240072 Hom.: 68 AF XY: 0.00491 AC XY: 637 AN XY: 129736

Gnomad AFR exome AF: 0.0915

Gnomad AMR exome AF: 0.00425

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000294

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000118

Gnomad OTH exome AF: 0.00256

GnomAD4 exome AF: 0.00256 AC: 3713 AN: 1447840 Hom.: 166 Cov.: 30 AF XY: 0.00228 AC XY: 1645 AN XY: 719980

Gnomad4 AFR exome AF: 0.0932

Gnomad4 AMR exome AF: 0.00455

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000266

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000759

Gnomad4 OTH exome AF: 0.00566

GnomAD4 genome AF: 0.0269 AC: 4100 AN: 152190 Hom.: 196 Cov.: 32 AF XY: 0.0265 AC XY: 1973 AN XY: 74414

Gnomad4 AFR AF: 0.0943

Gnomad4 AMR AF: 0.00837

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000191

Gnomad4 OTH AF: 0.0190

Alfa AF: 0.00483 Hom.: 53

Bravo AF: 0.0306

ESP6500AA AF: 0.0867 AC: 382

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.00813 AC: 987

Asia WGS AF: 0.00551 AC: 19 AN: 3460

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Apr 04, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	18
DANN	Benign	0.94
DEOGEN2	Benign	0.017	T;T;.
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.047
FATHMM_MKL	Benign	0.57	D
LIST_S2	Benign	0.72	T;T;T
MetaRNN	Benign	0.0014	T;T;T
MetaSVM	Benign	-1.2	T
MutationAssessor	Benign	0.55	N;.;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.18	N;.;N
REVEL	Benign	0.083
Sift	Benign	0.31	T;.;T
Sift4G	Benign	0.83	T;T;T
Polyphen		0.15	B;.;B
Vest4		0.066
MVP		0.18
MPC		0.19
ClinPred		0.012	T
GERP RS		4.4
Varity_R		0.056
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

Publications

LitVar

Other links and lift over

dbSNP: rs35829084; hg19: chr17-38027824;