chr14-39118015-C-A
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_003616.3(GEMIN2):c.239C>A(p.Pro80His) variant causes a missense change. The variant allele was found at a frequency of 0.0000175 in 1,600,688 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000099 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000090 ( 0 hom. )
Consequence
GEMIN2
NM_003616.3 missense
NM_003616.3 missense
Scores
16
3
Clinical Significance
Conservation
PhyloP100: 5.41
Genes affected
GEMIN2 (HGNC:10884): (gem nuclear organelle associated protein 2) This gene encodes one of the proteins found in the SMN complex, which consists of several gemin proteins and the protein known as the survival of motor neuron protein. The SMN complex is localized to a subnuclear compartment called gems (gemini of coiled bodies) and is required for assembly of spliceosomal snRNPs and for pre-mRNA splicing. This protein interacts directly with the survival of motor neuron protein and it is required for formation of the SMN complex. A knockout mouse targeting the mouse homolog of this gene exhibited disrupted snRNP assembly and motor neuron degeneration. [provided by RefSeq, Aug 2011]
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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;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GEMIN2 | NM_003616.3 | c.239C>A | p.Pro80His | missense_variant | 3/10 | ENST00000308317.12 | NP_003607.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
GEMIN2 | ENST00000308317.12 | c.239C>A | p.Pro80His | missense_variant | 3/10 | 1 | NM_003616.3 | ENSP00000308533 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000986 AC: 15AN: 152132Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00000811 AC: 2AN: 246546Hom.: 0 AF XY: 0.00000749 AC XY: 1AN XY: 133598
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GnomAD4 exome AF: 0.00000897 AC: 13AN: 1448556Hom.: 0 Cov.: 27 AF XY: 0.00000693 AC XY: 5AN XY: 721324
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GnomAD4 genome AF: 0.0000986 AC: 15AN: 152132Hom.: 0 Cov.: 33 AF XY: 0.0000673 AC XY: 5AN XY: 74296
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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 01, 2023 | The c.272C>A (p.P91H) alteration is located in exon 3 (coding exon 3) of the GEMIN2 gene. This alteration results from a C to A substitution at nucleotide position 272, causing the proline (P) at amino acid position 91 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
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
T
MetaRNN
Uncertain
D;D;D
MetaSVM
Uncertain
T
MutationAssessor
Uncertain
M;M;M
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D
REVEL
Uncertain
Sift
Uncertain
D;D;D
Sift4G
Uncertain
D;D;D
Polyphen
D;D;D
Vest4
MVP
MPC
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