7-76625627-G-C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_012230.5(POMZP3):​c.122C>G​(p.Pro41Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,638 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P41L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

POMZP3
NM_012230.5 missense

Scores

4
1
13

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.88

Publications

0 publications found
Variant links:
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]
LINC03009 (HGNC:56134): (long intergenic non-protein coding RNA 3009)

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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=0.33212954).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
POMZP3NM_012230.5 linkc.122C>G p.Pro41Arg missense_variant Exon 3 of 7 ENST00000310842.9 NP_036362.3 Q6PJE2-4
POMZP3NM_152992.4 linkc.122C>G p.Pro41Arg missense_variant Exon 3 of 5 NP_694537.1 Q6PJE2-5
LINC03009NR_029411.1 linkn.625-294G>C intron_variant Intron 2 of 2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
POMZP3ENST00000310842.9 linkc.122C>G p.Pro41Arg missense_variant Exon 3 of 7 1 NM_012230.5 ENSP00000309233.4 Q6PJE2-4

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1461638
Hom.:
0
Cov.:
35
AF XY:
0.00000138
AC XY:
1
AN XY:
727128
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33472
American (AMR)
AF:
0.00
AC:
0
AN:
44714
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26130
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39696
South Asian (SAS)
AF:
0.0000232
AC:
2
AN:
86250
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53418
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5762
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1111818
Other (OTH)
AF:
0.0000166
AC:
1
AN:
60378
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.442
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.14
BayesDel_addAF
Uncertain
0.014
T
BayesDel_noAF
Benign
-0.22
CADD
Benign
21
DANN
Benign
0.97
DEOGEN2
Benign
0.065
.;T;.
Eigen
Benign
0.091
Eigen_PC
Benign
-0.14
FATHMM_MKL
Benign
0.17
N
LIST_S2
Benign
0.78
T;T;T
M_CAP
Benign
0.013
T
MetaRNN
Benign
0.33
T;T;T
MetaSVM
Benign
-0.55
T
MutationAssessor
Pathogenic
3.0
M;M;.
PhyloP100
2.9
PROVEAN
Pathogenic
-6.1
D;N;D
REVEL
Benign
0.23
Sift
Pathogenic
0.0
D;D;D
Sift4G
Pathogenic
0.0
D;D;.
Polyphen
0.97
.;D;.
Vest4
0.59
MutPred
0.38
Loss of glycosylation at P41 (P = 0.0247);Loss of glycosylation at P41 (P = 0.0247);Loss of glycosylation at P41 (P = 0.0247);
MVP
0.26
MPC
1.6
ClinPred
0.99
D
GERP RS
0.36
PromoterAI
0.038
Neutral
Varity_R
0.46
gMVP
0.47
Mutation Taster
=93/7
polymorphism

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

Other links and lift over

dbSNP: rs745537336; hg19: chr7-76254944; COSMIC: COSV51885557; COSMIC: COSV51885557; API