NM_199321.3:c.519T>C

Variant names:

• chr17-39872382-T-C
• rs61737283
• NM_199321.3:c.519T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_199321.3(ZPBP2):​c.519T>C​(p.Ser173Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00489 in 1,613,512 control chromosomes in the GnomAD database, including 362 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.027 (189 hom., cov: 32)
  • Exomes 𝑓: 0.0026 (173 hom.)
• Consequence: ZPBP2 NM_199321.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.00500
• Publications: 3 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]

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 17-39872382-T-C is Benign according to our data. Variant chr17-39872382-T-C is described in ClinVar as Benign. ClinVar VariationId is 781283.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.005 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0912 is higher than 0.05.

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.519T>C	p.Ser173Ser	synonymous	Exon 5 of 8	NP_955353.1	Q6X784-1
	ZPBP2	NM_198844.3		c.453T>C	p.Ser151Ser	synonymous	Exon 4 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.519T>C	p.Ser173Ser	synonymous	Exon 5 of 8	ENSP00000335384.5	Q6X784-1
	ZPBP2	ENST00000377940.3	TSL:1	c.453T>C	p.Ser151Ser	synonymous	Exon 4 of 7	ENSP00000367174.3	Q6X784-2
	ZPBP2	ENST00000583811.5	TSL:3	c.165T>C	p.Ser55Ser	synonymous	Exon 2 of 5	ENSP00000462463.1	J3KSF6

Frequencies

GnomAD3 genomes AF: 0.0266 AC: 4053 AN: 152110 Hom.: 185 Cov.: 32

Gnomad AFR AF: 0.0935

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00832

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.0191

GnomAD2 exomes AF: 0.00670 AC: 1683 AN: 251142 AF XY: 0.00486

Gnomad AFR exome AF: 0.0924

Gnomad AMR exome AF: 0.00420

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000106

Gnomad OTH exome AF: 0.00261

GnomAD4 exome AF: 0.00262 AC: 3824 AN: 1461284 Hom.: 173 Cov.: 33 AF XY: 0.00230 AC XY: 1675 AN XY: 726976

African (AFR) AF: 0.0942 AC: 3150 AN: 33456

American (AMR) AF: 0.00463 AC: 207 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26116

East Asian (EAS) AF: 0.00 AC: 0 AN: 39598

South Asian (SAS) AF: 0.000267 AC: 23 AN: 86230

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53288

Middle Eastern (MID) AF: 0.00347 AC: 20 AN: 5760

European-Non Finnish (NFE) AF: 0.0000729 AC: 81 AN: 1111754

Other (OTH) AF: 0.00568 AC: 343 AN: 60376

GnomAD4 genome AF: 0.0267 AC: 4069 AN: 152228 Hom.: 189 Cov.: 32 AF XY: 0.0263 AC XY: 1957 AN XY: 74432

African (AFR) AF: 0.0936 AC: 3887 AN: 41514

American (AMR) AF: 0.00830 AC: 127 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000176 AC: 12 AN: 68002

Other (OTH) AF: 0.0189 AC: 40 AN: 2116

Alfa AF: 0.0213 Hom.: 103

Bravo AF: 0.0305

Asia WGS AF: 0.00550 AC: 19 AN: 3470

EpiCase AF: 0.0000546

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.1
DANN	Benign	0.63
PhyloP100		-0.0050
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs61737283; hg19: chr17-38028635;