chr7-75421613-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP2BP4
The NM_001099415.3(POM121C):c.2639C>T(p.Pro880Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000684 in 1,461,242 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: not found (cov: 33)
Exomes 𝑓: 0.0000068 ( 0 hom. )
Consequence
POM121C
NM_001099415.3 missense
NM_001099415.3 missense
Scores
2
13
Clinical Significance
Conservation
PhyloP100: 3.86
Genes affected
POM121C (HGNC:34005): (POM121 transmembrane nucleoporin C) Predicted to enable nuclear localization sequence binding activity. Predicted to be a structural constituent of nuclear pore. Predicted to be involved in RNA export from nucleus and protein import into nucleus. Predicted to be located in nuclear envelope. Predicted to be part of nuclear pore. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant in gene, where missense usually causes diseases (based on misZ statistic), POM121C. . Trascript score misZ 4.3224 (greater than threshold 3.09). GenCC has associacion of gene with schizophrenia.
BP4
Computational evidence support a benign effect (MetaRNN=0.27928853).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
POM121C | NM_001099415.3 | c.2639C>T | p.Pro880Leu | missense_variant | 13/15 | ENST00000615331.5 | NP_001092885.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
POM121C | ENST00000615331.5 | c.2639C>T | p.Pro880Leu | missense_variant | 13/15 | 1 | NM_001099415.3 | ENSP00000481575.1 | ||
POM121C | ENST00000607367.5 | c.3365C>T | p.Pro1122Leu | missense_variant | 11/13 | 5 | ENSP00000476236.2 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 250014Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135502
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GnomAD4 exome AF: 0.00000684 AC: 10AN: 1461242Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5AN XY: 726938
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GnomAD4 genome Cov.: 33
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33
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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 | Dec 08, 2023 | The c.2639C>T (p.P880L) alteration is located in exon 13 (coding exon 10) of the POM121C gene. This alteration results from a C to T substitution at nucleotide position 2639, causing the proline (P) at amino acid position 880 to be replaced by a leucine (L). 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
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
.;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Benign
T;T
M_CAP
Benign
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
PrimateAI
Benign
T
Sift4G
Uncertain
D;D
Polyphen
1.0
.;D
Vest4
MutPred
0.26
.;Loss of loop (P = 0.0374);
MVP
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at