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GeneBe

3-102477003-T-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001329788.2(ZPLD1):c.1043-9T>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00147 in 1,613,348 control chromosomes in the GnomAD database, including 60 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0017 ( 6 hom., cov: 32)
Exomes 𝑓: 0.0014 ( 54 hom. )

Consequence

ZPLD1
NM_001329788.2 splice_polypyrimidine_tract, intron

Scores

2
Splicing: ADA: 0.00005170
2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.860
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 3-102477003-T-A is Benign according to our data. Variant chr3-102477003-T-A is described in ClinVar as [Benign]. Clinvar id is 782809.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00174 (265/152224) while in subpopulation EAS AF= 0.0451 (234/5190). AF 95% confidence interval is 0.0404. There are 6 homozygotes in gnomad4. There are 149 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 6 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ZPLD1NM_001329788.2 linkuse as main transcriptc.1043-9T>A splice_polypyrimidine_tract_variant, intron_variant ENST00000466937.2
ZPLD1NM_175056.2 linkuse as main transcriptc.1091-9T>A splice_polypyrimidine_tract_variant, intron_variant
ZPLD1XM_017005703.1 linkuse as main transcriptc.1043-9T>A splice_polypyrimidine_tract_variant, intron_variant
ZPLD1XM_017005704.1 linkuse as main transcriptc.1043-9T>A splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ZPLD1ENST00000466937.2 linkuse as main transcriptc.1043-9T>A splice_polypyrimidine_tract_variant, intron_variant 1 NM_001329788.2 P1Q8TCW7-1
ZPLD1ENST00000306176.5 linkuse as main transcriptc.1091-9T>A splice_polypyrimidine_tract_variant, intron_variant 1 Q8TCW7-2
ZPLD1ENST00000491959.5 linkuse as main transcriptc.1043-9T>A splice_polypyrimidine_tract_variant, intron_variant 1 P1Q8TCW7-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00174
AC:
265
AN:
152106
Hom.:
6
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000555
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000262
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.0450
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00144
GnomAD3 exomes
AF:
0.00370
AC:
928
AN:
251000
Hom.:
23
AF XY:
0.00331
AC XY:
449
AN XY:
135644
show subpopulations
Gnomad AFR exome
AF:
0.000369
Gnomad AMR exome
AF:
0.000116
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0490
Gnomad SAS exome
AF:
0.000164
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00196
GnomAD4 exome
AF:
0.00144
AC:
2105
AN:
1461124
Hom.:
54
Cov.:
30
AF XY:
0.00140
AC XY:
1018
AN XY:
726890
show subpopulations
Gnomad4 AFR exome
AF:
0.0000598
Gnomad4 AMR exome
AF:
0.0000895
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.0474
Gnomad4 SAS exome
AF:
0.000267
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000126
Gnomad4 OTH exome
AF:
0.00300
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00174
AC:
265
AN:
152224
Hom.:
6
Cov.:
32
AF XY:
0.00200
AC XY:
149
AN XY:
74444
show subpopulations
Gnomad4 AFR
AF:
0.000553
Gnomad4 AMR
AF:
0.000262
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.0451
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00142
Alfa
AF:
0.000402
Hom.:
1
Bravo
AF:
0.00217
Asia WGS
AF:
0.0160
AC:
54
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeMay 25, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.81
Cadd
Benign
0.40
Dann
Benign
0.44

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.000052
dbscSNV1_RF
Benign
0.012
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.

Other links and lift over

dbSNP: rs58015062; hg19: chr3-102195847; API