rs864309486
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_StrongPM2PP5_Moderate
The NM_015895.5(GMNN):c.16A>T(p.Lys6Ter) variant causes a stop gained change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
GMNN
NM_015895.5 stop_gained
NM_015895.5 stop_gained
Scores
2
4
1
Clinical Significance
Conservation
PhyloP100: 4.51
Genes affected
GMNN (HGNC:17493): (geminin DNA replication inhibitor) This gene encodes a protein that plays a critical role in cell cycle regulation. The encoded protein inhibits DNA replication by binding to DNA replication factor Cdt1, preventing the incorporation of minichromosome maintenance proteins into the pre-replication complex. The encoded protein is expressed during the S and G2 phases of the cell cycle and is degraded by the anaphase-promoting complex during the metaphase-anaphase transition. Increased expression of this gene may play a role in several malignancies including colon, rectal and breast cancer. Alternatively spliced transcript variants have been observed for this gene, and two pseudogenes of this gene are located on the short arm of chromosome 16. [provided by RefSeq, Oct 2011]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 4 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 6-24777262-A-T is Pathogenic according to our data. Variant chr6-24777262-A-T is described in ClinVar as [Pathogenic]. Clinvar id is 203999.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-24777262-A-T is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GMNN | NM_015895.5 | c.16A>T | p.Lys6Ter | stop_gained | 2/7 | ENST00000230056.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GMNN | ENST00000230056.8 | c.16A>T | p.Lys6Ter | stop_gained | 2/7 | 1 | NM_015895.5 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1261074Hom.: 0 Cov.: 18 AF XY: 0.00 AC XY: 0AN XY: 635082
GnomAD4 exome
Data not reliable, filtered out with message: AC0
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0
AN:
1261074
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Cov.:
18
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0
AN XY:
635082
Gnomad4 AFR exome
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Meier-Gorlin syndrome Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Jun 17, 2015 | This nonsense variant was found once in our laboratory de novo in a 2-year-old female with Meier-Gorlin syndrome - |
Meier-Gorlin syndrome 6 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Dec 03, 2015 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
MutationTaster
Benign
A;A
Vest4
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
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Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DL_spliceai
Position offset: 35
Find out detailed SpliceAI scores and Pangolin per-transcript scores at