Variant 3-102464227-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001329788.2(ZPLD1):c.737A>G(p.Asp246Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000242 in 1,612,680 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

ZPLD1
NM_001329788.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.11

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2630576).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ZPLD1	NM_001329788.2 linkuse as main transcript	c.737A>G	p.Asp246Gly	missense_variant	8/12	ENST00000466937.2
ZPLD1	NM_175056.2 linkuse as main transcript	c.785A>G	p.Asp262Gly	missense_variant	7/11
ZPLD1	XM_017005703.1 linkuse as main transcript	c.737A>G	p.Asp246Gly	missense_variant	8/12
ZPLD1	XM_017005704.1 linkuse as main transcript	c.737A>G	p.Asp246Gly	missense_variant	7/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZPLD1	ENST00000466937.2 linkuse as main transcript	c.737A>G	p.Asp246Gly	missense_variant	8/12	1	NM_001329788.2	P1	Q8TCW7-1
ZPLD1	ENST00000306176.5 linkuse as main transcript	c.785A>G	p.Asp262Gly	missense_variant	7/11	1			Q8TCW7-2
ZPLD1	ENST00000491959.5 linkuse as main transcript	c.737A>G	p.Asp246Gly	missense_variant	14/18	1		P1	Q8TCW7-1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152242

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251252

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135794

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.0000264

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000253

AC:

AN:

1460438

Hom.:

Cov.:

AF XY:

0.0000289

AC XY:

AN XY:

726650

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.0000324

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152242

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000693

Hom.:

Bravo

AF:

0.0000302

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

May 11, 2022

The c.785A>G (p.D262G) alteration is located in exon 7 (coding exon 7) of the ZPLD1 gene. This alteration results from a A to G substitution at nucleotide position 785, causing the aspartic acid (D) at amino acid position 262 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

0.11

BayesDel_addAF

Benign

-0.0037

BayesDel_noAF

Benign

-0.23

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.14

T;.;T

Eigen

Benign

-0.14

Eigen_PC

Benign

0.039

FATHMM_MKL

Uncertain

0.97

M_CAP

Benign

0.045

MetaRNN

Benign

0.26

T;T;T

MetaSVM

Benign

-0.56

MutationAssessor

Benign

1.5

L;.;L

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-1.9

N;N;N

REVEL

Benign

0.23

Sift

Benign

0.14

T;T;T

Sift4G

Uncertain

0.014

D;D;D

Polyphen

0.0

B;B;B

Vest4

0.34

MVP

0.82

MPC

0.097

ClinPred

0.40

GERP RS

4.4

Varity_R

0.23

gMVP

0.42

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

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