3-102477605-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001329788.2(ZPLD1):c.1235C>G(p.Pro412Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZPLD1 NM_001329788.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.62

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZPLD1	NM_001329788.2	c.1235C>G	p.Pro412Arg	missense_variant	12/12	ENST00000466937.2
ZPLD1	NM_175056.2	c.1283C>G	p.Pro428Arg	missense_variant	11/11
ZPLD1	XM_017005703.1	c.1235C>G	p.Pro412Arg	missense_variant	12/12
ZPLD1	XM_017005704.1	c.1235C>G	p.Pro412Arg	missense_variant	11/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZPLD1	ENST00000466937.2	c.1235C>G	p.Pro412Arg	missense_variant	12/12	1	NM_001329788.2	P1
ZPLD1	ENST00000306176.5	c.1283C>G	p.Pro428Arg	missense_variant	11/11	1
ZPLD1	ENST00000491959.5	c.1235C>G	p.Pro412Arg	missense_variant	18/18	1		P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 29, 2023

The c.1283C>G (p.P428R) alteration is located in exon 11 (coding exon 11) of the ZPLD1 gene. This alteration results from a C to G substitution at nucleotide position 1283, causing the proline (P) at amino acid position 428 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.17
Cadd	Uncertain	26
Dann	Uncertain	1.0
DEOGEN2	Benign	0.023	T;.;T
Eigen	Uncertain	0.67
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Pathogenic	0.99	D
M_CAP	Uncertain	0.097	D
MetaRNN	Uncertain	0.60	D;D;D
MetaSVM	Uncertain	0.20	D
MutationAssessor	Benign	2.0	M;.;M
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-0.42	N;N;N
REVEL	Uncertain	0.49
Sift	Uncertain	0.014	D;D;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		1.0	D;D;D
Vest4		0.46
MutPred		0.50		Gain of MoRF binding (P = 0.0054);.;Gain of MoRF binding (P = 0.0054);
MVP		0.93
MPC		0.37
ClinPred		0.98	D
GERP RS		6.0
Varity_R		0.18
gMVP		0.86

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-102196449;