NM_012230.5:c.332A>T
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_012230.5(POMZP3):c.332A>T(p.Asp111Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 24)
Exomes 𝑓: 0.000011 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
POMZP3
NM_012230.5 missense
NM_012230.5 missense
Scores
6
12
Clinical Significance
Conservation
PhyloP100: 2.24
Publications
0 publications found
Genes affected
POMZP3 (HGNC:9203): (POM121 and ZP3 fusion) This gene appears to have resulted from a fusion of DNA sequences derived from 2 distinct loci, specifically through the duplication of two internal exons from the POM121 gene and four 3' exons from the ZP3 gene. The 5' end of this gene is similar to the 5` coding region of the POM121 gene which encodes an integral nuclear pore membrane protein. However, the protein encoded by this gene lacks the nuclear pore localization motif. The 3' end of this gene is similar to the last 4 exons of the zona pellucida glycoprotein 3 (ZP3) gene and the encoded protein retains one zona pellucida domain. Multiple protein isoforms are encoded by transcript variants of this gene. [provided by RefSeq, Jul 2008]
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.24401012).
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| POMZP3 | NM_012230.5 | c.332A>T | p.Asp111Val | missense_variant | Exon 4 of 7 | ENST00000310842.9 | NP_036362.3 | |
| POMZP3 | NM_152992.4 | c.332A>T | p.Asp111Val | missense_variant | Exon 4 of 5 | NP_694537.1 | ||
| LINC03009 | NR_029411.1 | n.625-7725T>A | intron_variant | Intron 2 of 2 |
Ensembl
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
24
GnomAD2 exomes AF: 0.0000166 AC: 4AN: 240306 AF XY: 0.00 show subpopulations
GnomAD2 exomes
AF:
AC:
4
AN:
240306
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000110 AC: 16AN: 1459090Hom.: 0 Cov.: 30 AF XY: 0.00000689 AC XY: 5AN XY: 725864 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
AC:
16
AN:
1459090
Hom.:
Cov.:
30
AF XY:
AC XY:
5
AN XY:
725864
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
33436
American (AMR)
AF:
AC:
0
AN:
44698
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26102
East Asian (EAS)
AF:
AC:
0
AN:
39680
South Asian (SAS)
AF:
AC:
0
AN:
86202
European-Finnish (FIN)
AF:
AC:
0
AN:
53376
Middle Eastern (MID)
AF:
AC:
0
AN:
5754
European-Non Finnish (NFE)
AF:
AC:
14
AN:
1109548
Other (OTH)
AF:
AC:
2
AN:
60294
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.347
Heterozygous variant carriers
0
2
3
5
6
8
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
GnomAD4 genome
Cov.:
24
Alfa
AF:
Hom.:
ExAC
AF:
AC:
2
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Oct 20, 2023
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing
The c.332A>T (p.D111V) alteration is located in exon 4 (coding exon 3) of the POMZP3 gene. This alteration results from a A to T substitution at nucleotide position 332, causing the aspartic acid (D) at amino acid position 111 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
DANN
Benign
DEOGEN2
Uncertain
.;D;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;.
PhyloP100
PROVEAN
Uncertain
D;D;D
REVEL
Benign
Sift
Uncertain
D;D;D
Sift4G
Uncertain
D;D;.
Polyphen
0.85
.;P;.
Vest4
MutPred
Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);.;
MVP
MPC
3.2
ClinPred
T
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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