Variant chr17-39872276-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_199321.3(ZPBP2):c.413G>A(p.Arg138Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000768 in 1,431,754 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000077 ( 0 hom. )

Consequence

ZPBP2
NM_199321.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.47

Variant links:

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]

ZPBP2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3371306).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ZPBP2	NM_199321.3 linkuse as main transcript	c.413G>A	p.Arg138Gln	missense_variant	5/8	ENST00000348931.9	NP_955353.1
ZPBP2	NM_198844.3 linkuse as main transcript	c.347G>A	p.Arg116Gln	missense_variant	4/7		NP_942141.2
ZPBP2	XM_047435318.1 linkuse as main transcript	c.413G>A	p.Arg138Gln	missense_variant	5/7		XP_047291274.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZPBP2	ENST00000348931.9 linkuse as main transcript	c.413G>A	p.Arg138Gln	missense_variant	5/8	1	NM_199321.3	ENSP00000335384	P1	Q6X784-1
ZPBP2	ENST00000377940.3 linkuse as main transcript	c.347G>A	p.Arg116Gln	missense_variant	4/7	1		ENSP00000367174		Q6X784-2
ZPBP2	ENST00000583811.5 linkuse as main transcript	c.59G>A	p.Arg20Gln	missense_variant	2/5	3		ENSP00000462463
ZPBP2	ENST00000584588.5 linkuse as main transcript	c.406+651G>A		intron_variant		5		ENSP00000462067

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000442

AC:

AN:

226362

Hom.:

AF XY:

0.00000815

AC XY:

AN XY:

122732

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000948

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000768

AC:

AN:

1431754

Hom.:

Cov.:

AF XY:

0.00000562

AC XY:

AN XY:

711576

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000263

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:

0.00000818

Gnomad4 OTH exome

AF:

0.0000170

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000377

Hom.:

Bravo

AF:

0.0000189

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 11, 2024

The c.413G>A (p.R138Q) alteration is located in exon 5 (coding exon 5) of the ZPBP2 gene. This alteration results from a G to A substitution at nucleotide position 413, causing the arginine (R) at amino acid position 138 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.043

BayesDel_noAF

Benign

-0.30

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.12

T;.;.

Eigen

Uncertain

0.42

Eigen_PC

Uncertain

0.46

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.79

T;T;T

M_CAP

Benign

0.053

MetaRNN

Benign

0.34

T;T;T

MetaSVM

Benign

-0.57

MutationAssessor

Benign

0.84

L;.;.

MutationTaster

Benign

1.0

D;N;N

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.6

N;.;N

REVEL

Benign

0.24

Sift

Benign

0.064

T;.;T

Sift4G

Benign

0.10

T;T;T

Polyphen

0.98

D;.;P

Vest4

0.41

MVP

0.23

MPC

0.44

ClinPred

0.69

GERP RS

4.3

Varity_R

0.12

gMVP

0.57

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.17

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over