17-39868375-A-C

Variant names:

• chr17-39868375-A-C
• NM_199321.3:c.21A>C
• ZPBP2 p.Leu7Leu

Variant summary

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

The NM_199321.3(ZPBP2):​c.21A>C​(p.Leu7Leu) 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.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZPBP2 NM_199321.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.90
• Publications: 0 publications found

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]

ENSG00000302760 (HGNC:):

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=-0.85).
• BP7: Synonymous conserved (PhyloP=-2.9 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_199321.3. 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
	ZPBP2	NM_199321.3	MANE Select	c.21A>C	p.Leu7Leu	synonymous	Exon 1 of 8	NP_955353.1	Q6X784-1
	ZPBP2	NM_198844.3		c.21A>C	p.Leu7Leu	synonymous	Exon 1 of 7	NP_942141.2	Q6X784-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZPBP2	ENST00000348931.9	TSL:1 MANE Select	c.21A>C	p.Leu7Leu	synonymous	Exon 1 of 8	ENSP00000335384.5	Q6X784-1
	ZPBP2	ENST00000377940.3	TSL:1	c.21A>C	p.Leu7Leu	synonymous	Exon 1 of 7	ENSP00000367174.3	Q6X784-2
	ZPBP2	ENST00000584588.5	TSL:5	c.21A>C	p.Leu7Leu	synonymous	Exon 1 of 7	ENSP00000462067.1	J3KRM0

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.19
DANN	Benign	0.53
PhyloP100		-2.9
PromoterAI		0.015	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: chr17-38024628;