NM_007009.3:c.375T>G

Variant names:

• chr7-50058101-A-C
• NM_007009.3:c.375T>G
• ZPBP p.Leu125Leu

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_007009.3(ZPBP):​c.375T>G​(p.Leu125Leu) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L125L) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZPBP NM_007009.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.268
• 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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP7: Synonymous conserved (PhyloP=0.268 with no splicing effect.

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.375T>G	p.Leu125Leu	synonymous	Exon 4 of 8	NP_008940.2	Q9BS86-1
	ZPBP	NM_001159878.2		c.372T>G	p.Leu124Leu	synonymous	Exon 4 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.375T>G	p.Leu125Leu	synonymous	Exon 4 of 8	ENSP00000046087.2	Q9BS86-1
	ZPBP	ENST00000419417.5	TSL:1	c.372T>G	p.Leu124Leu	synonymous	Exon 4 of 8	ENSP00000402071.1	Q9BS86-2
	ZPBP	ENST00000903719.1		c.375T>G	p.Leu125Leu	synonymous	Exon 4 of 6	ENSP00000573778.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	6.7
DANN	Benign	0.76
PhyloP100		0.27

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr7-50097697;