dbSNP rs139821068: ZPLD1:p.Arg273Gln (chr3-102469020-G-A) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001329788.2(ZPLD1):c.818G>A(p.Arg273Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000372 in 1,614,038 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

ZPLD1
NM_001329788.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.91

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 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.81

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZPLD1	NM_001329788.2 link	c.818G>A	p.Arg273Gln	missense_variant	Exon 9 of 12	ENST00000466937.2	NP_001316717.1	Q8TCW7-1
ZPLD1	NM_175056.2 link	c.866G>A	p.Arg289Gln	missense_variant	Exon 8 of 11		NP_778226.1	Q8TCW7-2
ZPLD1	XM_017005703.1 link	c.818G>A	p.Arg273Gln	missense_variant	Exon 9 of 12		XP_016861192.1	Q8TCW7-1
ZPLD1	XM_017005704.1 link	c.818G>A	p.Arg273Gln	missense_variant	Exon 8 of 11		XP_016861193.1	Q8TCW7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ZPLD1	ENST00000466937.2 link	c.818G>A	p.Arg273Gln	missense_variant	Exon 9 of 12	1	NM_001329788.2	ENSP00000418253.1	Q8TCW7-1
ZPLD1	ENST00000306176.5 link	c.866G>A	p.Arg289Gln	missense_variant	Exon 8 of 11	1		ENSP00000307801.1	Q8TCW7-2
ZPLD1	ENST00000491959.5 link	c.818G>A	p.Arg273Gln	missense_variant	Exon 15 of 18	1		ENSP00000420265.1	Q8TCW7-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152154

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:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

250808

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135664

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461766

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727176

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152272

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Pathogenic

0.19

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.39

T;.;T

Eigen

Pathogenic

0.69

Eigen_PC

Pathogenic

0.69

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.94

.;D;D

M_CAP

Uncertain

0.10

MetaRNN

Pathogenic

0.81

D;D;D

MetaSVM

Uncertain

0.45

MutationAssessor

Uncertain

2.2

M;.;M

PrimateAI

Uncertain

0.65

PROVEAN

Uncertain

-2.8

D;D;D

REVEL

Pathogenic

0.71

Sift

Uncertain

0.0060

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

0.99

D;D;D

Vest4

0.80

MVP

0.83

MPC

0.29

ClinPred

0.99

GERP RS

5.5

Varity_R

0.44

gMVP

0.69

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over