3-102141716-T-C

Variant names:

• chr3-102141716-T-C
• rs938988
• ENST00000491959.5:c.-779+40145T>C

Variant summary

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

The ENST00000491959.5(ZPLD1):​c.-779+40145T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.676 in 152,032 control chromosomes in the GnomAD database, including 35,427 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 0.68 (35427 hom., cov: 31)
• Consequence: ZPLD1 ENST00000491959.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.163
• Publications: 3 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.939 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+40145T>C		intron_variant	Intron 2 of 17	1		ENSP00000420265.1

Frequencies

GnomAD3 genomes AF: 0.676 AC: 102655 AN: 151914 Hom.: 35402 Cov.: 31

Gnomad AFR AF: 0.560

Gnomad AMI AF: 0.730

Gnomad AMR AF: 0.784

Gnomad ASJ AF: 0.665

Gnomad EAS AF: 0.961

Gnomad SAS AF: 0.703

Gnomad FIN AF: 0.627

Gnomad MID AF: 0.748

Gnomad NFE AF: 0.704

Gnomad OTH AF: 0.711

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

GnomAD4 genome AF: 0.676 AC: 102729 AN: 152032 Hom.: 35427 Cov.: 31 AF XY: 0.678 AC XY: 50376 AN XY: 74304

African (AFR) AF: 0.560 AC: 23205 AN: 41440

American (AMR) AF: 0.784 AC: 11974 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.665 AC: 2310 AN: 3472

East Asian (EAS) AF: 0.961 AC: 4972 AN: 5174

South Asian (SAS) AF: 0.703 AC: 3386 AN: 4814

European-Finnish (FIN) AF: 0.627 AC: 6617 AN: 10558

Middle Eastern (MID) AF: 0.757 AC: 221 AN: 292

European-Non Finnish (NFE) AF: 0.704 AC: 47875 AN: 67992

Other (OTH) AF: 0.713 AC: 1505 AN: 2110

Alfa AF: 0.702 Hom.: 158303

Bravo AF: 0.684

Asia WGS AF: 0.804 AC: 2795 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.1
DANN	Benign	0.53
PhyloP100		0.16
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: rs938988; hg19: chr3-101860560;