Variant 3-102452933-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001329788.2(ZPLD1):c.121A>G(p.Ser41Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,664 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

ZPLD1
NM_001329788.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.84

Variant links:

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]

ZPLD1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.28497308).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZPLD1	NM_001329788.2 linkuse as main transcript	c.121A>G	p.Ser41Gly	missense_variant	4/12	ENST00000466937.2	NP_001316717.1	Q8TCW7-1
ZPLD1	NM_175056.2 linkuse as main transcript	c.169A>G	p.Ser57Gly	missense_variant	3/11		NP_778226.1	Q8TCW7-2
ZPLD1	XM_017005703.1 linkuse as main transcript	c.121A>G	p.Ser41Gly	missense_variant	4/12		XP_016861192.1	Q8TCW7-1
ZPLD1	XM_017005704.1 linkuse as main transcript	c.121A>G	p.Ser41Gly	missense_variant	3/11		XP_016861193.1	Q8TCW7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZPLD1	ENST00000466937.2 linkuse as main transcript	c.121A>G	p.Ser41Gly	missense_variant	4/12	1	NM_001329788.2	ENSP00000418253.1	Q8TCW7-1
ZPLD1	ENST00000306176.5 linkuse as main transcript	c.169A>G	p.Ser57Gly	missense_variant	3/11	1		ENSP00000307801.1	Q8TCW7-2
ZPLD1	ENST00000491959.5 linkuse as main transcript	c.121A>G	p.Ser41Gly	missense_variant	10/18	1		ENSP00000420265.1	Q8TCW7-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000199

AC:

AN:

251136

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135718

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1461664

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727118

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000179

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000151

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 02, 2023

The c.169A>G (p.S57G) alteration is located in exon 3 (coding exon 3) of the ZPLD1 gene. This alteration results from a A to G substitution at nucleotide position 169, causing the serine (S) at amino acid position 57 to be replaced by a glycine (G). 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

0.12

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.22

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.061

T;.;T

Eigen

Benign

0.068

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.90

.;D;D

M_CAP

Benign

0.022

MetaRNN

Benign

0.28

T;T;T

MetaSVM

Benign

-0.56

MutationAssessor

Uncertain

2.2

M;.;M

PrimateAI

Benign

0.33

PROVEAN

Benign

-2.3

N;N;N

REVEL

Benign

0.28

Sift

Benign

0.18

T;T;T

Sift4G

Uncertain

0.034

D;D;D

Polyphen

0.046

B;B;B

Vest4

0.50

MutPred

0.42

Gain of catalytic residue at S41 (P = 0.0061);.;Gain of catalytic residue at S41 (P = 0.0061);

MVP

0.71

MPC

0.072

ClinPred

0.38

GERP RS

6.0

Varity_R

0.21

gMVP

0.53

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over