NM_012230.5:c.349T>C
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4
The NM_012230.5(POMZP3):c.349T>C(p.Tyr117His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000547 in 1,573,522 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000055 ( 0 hom., cov: 23)
Exomes 𝑓: 0.000055 ( 0 hom. )
Consequence
POMZP3
NM_012230.5 missense
NM_012230.5 missense
Scores
4
8
6
Clinical Significance
Conservation
PhyloP100: 3.33
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 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.2700395).
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| POMZP3 | NM_012230.5 | c.349T>C | p.Tyr117His | missense_variant | Exon 5 of 7 | ENST00000310842.9 | NP_036362.3 | |
| POMZP3 | NM_152992.4 | c.346-1595T>C | intron_variant | Intron 4 of 4 | NP_694537.1 | |||
| LINC03009 | NR_029411.1 | n.625-14111A>G | intron_variant | Intron 2 of 2 |
Ensembl
Frequencies
GnomAD3 genomes 0.0000546 AC: 8AN: 146390Hom.: 0 Cov.: 23 show subpopulations
GnomAD3 genomes
AF:
AC:
8
AN:
146390
Hom.:
Cov.:
23
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD2 exomes AF: 0.0000817 AC: 19AN: 232658 AF XY: 0.0000799 show subpopulations
GnomAD2 exomes
AF:
AC:
19
AN:
232658
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 AF: 0.0000547 AC: 78AN: 1427026Hom.: 0 Cov.: 32 AF XY: 0.0000564 AC XY: 40AN XY: 709108 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
78
AN:
1427026
Hom.:
Cov.:
32
AF XY:
AC XY:
40
AN XY:
709108
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
1
AN:
32508
American (AMR)
AF:
AC:
0
AN:
43548
Ashkenazi Jewish (ASJ)
AF:
AC:
6
AN:
24898
East Asian (EAS)
AF:
AC:
2
AN:
39658
South Asian (SAS)
AF:
AC:
0
AN:
84136
European-Finnish (FIN)
AF:
AC:
22
AN:
52792
Middle Eastern (MID)
AF:
AC:
0
AN:
4962
European-Non Finnish (NFE)
AF:
AC:
45
AN:
1085468
Other (OTH)
AF:
AC:
2
AN:
59056
⚠️ 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: 0.377
Heterozygous variant carriers
0
4
8
11
15
19
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome 0.0000546 AC: 8AN: 146496Hom.: 0 Cov.: 23 AF XY: 0.0000420 AC XY: 3AN XY: 71458 show subpopulations ⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
GnomAD4 genome
AF:
AC:
8
AN:
146496
Hom.:
Cov.:
23
AF XY:
AC XY:
3
AN XY:
71458
show subpopulations
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
38574
American (AMR)
AF:
AC:
0
AN:
14746
Ashkenazi Jewish (ASJ)
AF:
AC:
2
AN:
3402
East Asian (EAS)
AF:
AC:
0
AN:
5112
South Asian (SAS)
AF:
AC:
0
AN:
4620
European-Finnish (FIN)
AF:
AC:
2
AN:
10378
Middle Eastern (MID)
AF:
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
AC:
4
AN:
66522
Other (OTH)
AF:
AC:
0
AN:
1966
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.004306), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.394
Heterozygous variant carriers
0
1
2
2
3
4
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
ESP6500AA
AF:
AC:
1
ESP6500EA
AF:
AC:
0
ExAC
AF:
AC:
12
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Apr 15, 2024
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing
The c.349T>C (p.Y117H) alteration is located in exon 5 (coding exon 4) of the POMZP3 gene. This alteration results from a T to C substitution at nucleotide position 349, causing the tyrosine (Y) at amino acid position 117 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
D;.
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Uncertain
D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
M;.
PhyloP100
PROVEAN
Uncertain
D;N
REVEL
Pathogenic
Sift
Pathogenic
D;D
Sift4G
Benign
T;.
Polyphen
D;.
Vest4
MVP
MPC
ClinPred
D
GERP RS
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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