rs10212363

Variant names:

• chr3-102129717-G-A
• rs10212363
• ENST00000491959.5:c.-779+28146G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000491959.5(ZPLD1):​c.-779+28146G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 152,030 control chromosomes in the GnomAD database, including 3,266 homozygotes. 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: 𝑓 0.21 (3266 hom., cov: 32)
• Consequence: ZPLD1 ENST00000491959.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.141
• Publications: 7 publications found

Genes affected

ZPLD1 (HGNC:27022): (zona pellucida like domain containing 1) Predicted to be an extracellular matrix structural constituent. Predicted to act upstream of or within vestibular reflex. Predicted to be located in cytoplasmic vesicle membrane. Predicted to be integral component of membrane. Predicted to be active in cell surface and extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.229 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZPLD1	ENST00000491959.5	c.-779+28146G>A		intron_variant	Intron 2 of 17	1		ENSP00000420265.1

Frequencies

GnomAD3 genomes AF: 0.206 AC: 31322 AN: 151912 Hom.: 3262 Cov.: 32

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.188

Gnomad AMR AF: 0.235

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.126

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.203

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.219

Gnomad OTH AF: 0.210

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.206 AC: 31344 AN: 152030 Hom.: 3266 Cov.: 32 AF XY: 0.204 AC XY: 15130 AN XY: 74304

African (AFR) AF: 0.195 AC: 8096 AN: 41464

American (AMR) AF: 0.235 AC: 3585 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.173 AC: 601 AN: 3468

East Asian (EAS) AF: 0.126 AC: 654 AN: 5178

South Asian (SAS) AF: 0.145 AC: 701 AN: 4824

European-Finnish (FIN) AF: 0.203 AC: 2145 AN: 10584

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.219 AC: 14874 AN: 67958

Other (OTH) AF: 0.212 AC: 445 AN: 2104

Alfa AF: 0.206 Hom.: 1818

Bravo AF: 0.207

Asia WGS AF: 0.167 AC: 582 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.90
DANN	Benign	0.54
PhyloP100		-0.14
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: rs10212363; hg19: chr3-101848561;