NM_007009.3:c.832G>A

Variant names:

• chr7-49983471-C-T
• rs144764759
• NM_007009.3:c.832G>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_007009.3(ZPBP):​c.832G>A​(p.Gly278Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000119 in 1,609,944 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000099 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00012 (0 hom.)
• Consequence: ZPBP NM_007009.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.37
• Publications: 0 publications found

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]

ZPBP Gene-Disease associations (from GenCC):

• spermatogenic failure 66

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.3218845).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007009.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZPBP	NM_007009.3	MANE Select	c.832G>A	p.Gly278Ser	missense	Exon 7 of 8	NP_008940.2	Q9BS86-1
	ZPBP	NM_001159878.2		c.829G>A	p.Gly277Ser	missense	Exon 7 of 8	NP_001153350.1	Q9BS86-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZPBP	ENST00000046087.7	TSL:1 MANE Select	c.832G>A	p.Gly278Ser	missense	Exon 7 of 8	ENSP00000046087.2	Q9BS86-1
	ZPBP	ENST00000419417.5	TSL:1	c.829G>A	p.Gly277Ser	missense	Exon 7 of 8	ENSP00000402071.1	Q9BS86-2
	ZPBP	ENST00000903720.1		c.460G>A	p.Gly154Ser	missense	Exon 5 of 7	ENSP00000573779.1

Frequencies

GnomAD3 genomes AF: 0.0000988 AC: 15 AN: 151898 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000656

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: 0.000132

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000401 AC: 10 AN: 249188 AF XY: 0.0000297

Gnomad AFR exome AF: 0.000186

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000619

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000121 AC: 177 AN: 1458046 Hom.: 0 Cov.: 29 AF XY: 0.000114 AC XY: 83 AN XY: 725336

African (AFR) AF: 0.0000899 AC: 3 AN: 33386

American (AMR) AF: 0.00 AC: 0 AN: 44474

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26072

East Asian (EAS) AF: 0.00 AC: 0 AN: 39540

South Asian (SAS) AF: 0.00 AC: 0 AN: 85524

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53286

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5746

European-Non Finnish (NFE) AF: 0.000156 AC: 173 AN: 1109746

Other (OTH) AF: 0.0000166 AC: 1 AN: 60272

GnomAD4 genome AF: 0.0000988 AC: 15 AN: 151898 Hom.: 0 Cov.: 32 AF XY: 0.0000270 AC XY: 2 AN XY: 74162

African (AFR) AF: 0.000121 AC: 5 AN: 41354

American (AMR) AF: 0.0000656 AC: 1 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10570

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

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 67958

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

Alfa AF: 0.0000868 Hom.: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.0000330 AC: 4

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	T
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Benign	0.56	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.0087	T
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-0.67	T
MutationAssessor	Benign	2.0	M
PhyloP100		2.4
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.15
Sift	Benign	0.49	T
Sift4G	Benign	0.068	T
Polyphen		1.0	D
Vest4		0.42
MVP		0.60
MPC		0.68
ClinPred		0.30	T
GERP RS		5.7
Varity_R		0.080
gMVP		0.45
Mutation Taster		=91/9	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs144764759; hg19: chr7-50023067;