Variant 3-102469122-C-A 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.920C>A(p.Pro307His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,540 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: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

ZPLD1
NM_001329788.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.23

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:

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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=0.25909877).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZPLD1	NM_001329788.2 linkuse as main transcript	c.920C>A	p.Pro307His	missense_variant	9/12	ENST00000466937.2	NP_001316717.1	Q8TCW7-1
ZPLD1	NM_175056.2 linkuse as main transcript	c.968C>A	p.Pro323His	missense_variant	8/11		NP_778226.1	Q8TCW7-2
ZPLD1	XM_017005703.1 linkuse as main transcript	c.920C>A	p.Pro307His	missense_variant	9/12		XP_016861192.1	Q8TCW7-1
ZPLD1	XM_017005704.1 linkuse as main transcript	c.920C>A	p.Pro307His	missense_variant	8/11		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.920C>A	p.Pro307His	missense_variant	9/12	1	NM_001329788.2	ENSP00000418253.1	Q8TCW7-1
ZPLD1	ENST00000306176.5 linkuse as main transcript	c.968C>A	p.Pro323His	missense_variant	8/11	1		ENSP00000307801.1	Q8TCW7-2
ZPLD1	ENST00000491959.5 linkuse as main transcript	c.920C>A	p.Pro307His	missense_variant	15/18	1		ENSP00000420265.1	Q8TCW7-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.86e-7

AC:

AN:

1458540

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725494

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:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Jan 04, 2024

The c.968C>A (p.P323H) alteration is located in exon 8 (coding exon 8) of the ZPLD1 gene. This alteration results from a C to A substitution at nucleotide position 968, causing the proline (P) at amino acid position 323 to be replaced by a histidine (H). 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

0.14

BayesDel_addAF

Uncertain

0.030

BayesDel_noAF

Benign

-0.19

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.012

T;.;T

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.17

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.82

.;T;T

M_CAP

Benign

0.041

MetaRNN

Benign

0.26

T;T;T

MetaSVM

Benign

-0.51

MutationAssessor

Uncertain

2.2

M;.;M

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-1.6

N;N;N

REVEL

Benign

0.26

Sift

Benign

0.10

T;T;T

Sift4G

Benign

0.25

T;T;T

Polyphen

0.019

B;B;B

Vest4

0.53

MutPred

0.44

Loss of sheet (P = 0.0817);.;Loss of sheet (P = 0.0817);

MVP

0.70

MPC

0.088

ClinPred

0.35

GERP RS

4.6

Varity_R

0.17

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over