chr7-50018292-C-A
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_007009.3(ZPBP):c.731G>T(p.Gly244Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000041 in 1,609,624 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000043 ( 0 hom. )
Consequence
ZPBP
NM_007009.3 missense
NM_007009.3 missense
Scores
4
15
Clinical Significance
Conservation
PhyloP100: 0.863
Genes affected
ZPBP (HGNC:15662): (zona pellucida binding protein) ZPBP is one of several proteins that are thought to participate in secondary binding between acrosome-reacted sperm and the egg-specific extracellular matrix, the zona pellucida (McLeskey et al., 1998 [PubMed 9378618]).[supplied by OMIM, Aug 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ZPBP | ENST00000046087.7 | c.731G>T | p.Gly244Val | missense_variant | 6/8 | 1 | NM_007009.3 | ENSP00000046087.2 | ||
ZPBP | ENST00000419417.5 | c.728G>T | p.Gly243Val | missense_variant | 6/8 | 1 | ENSP00000402071.1 | |||
ZPBP | ENST00000491129.5 | n.241-34773G>T | intron_variant | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000198 AC: 3AN: 151618Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000440 AC: 11AN: 250254Hom.: 0 AF XY: 0.0000444 AC XY: 6AN XY: 135276
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GnomAD4 exome AF: 0.0000432 AC: 63AN: 1458006Hom.: 0 Cov.: 30 AF XY: 0.0000372 AC XY: 27AN XY: 725418
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GnomAD4 genome AF: 0.0000198 AC: 3AN: 151618Hom.: 0 Cov.: 32 AF XY: 0.0000270 AC XY: 2AN XY: 74010
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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 | Oct 01, 2024 | The c.731G>T (p.G244V) alteration is located in exon 6 (coding exon 6) of the ZPBP gene. This alteration results from a G to T substitution at nucleotide position 731, causing the glycine (G) at amino acid position 244 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Benign
D
LIST_S2
Benign
T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.
PrimateAI
Benign
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
D;.
Vest4
MutPred
Gain of methylation at K243 (P = 0.0446);.;
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AL_spliceai
Position offset: 24
Find out detailed SpliceAI scores and Pangolin per-transcript scores at