rs147175353
Positions:
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2
The NM_032575.3(GLIS2):c.415G>A(p.Gly139Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00059 in 1,612,616 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0028 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00036 ( 2 hom. )
Consequence
GLIS2
NM_032575.3 missense
NM_032575.3 missense
Scores
5
12
Clinical Significance
Conservation
PhyloP100: 5.88
Genes affected
GLIS2 (HGNC:29450): (GLIS family zinc finger 2) This gene is a member of the GLI-similar zinc finger protein family and encodes a nuclear transcription factor with five C2H2-type zinc finger domains. The protein encoded by this gene is widely expressed at low levels in the neural tube and peripheral nervous system and likely promotes neuronal differentiation. It is abundantly expressed in the kidney and may have a role in the regulation of kidney morphogenesis. p120 regulates the expression level of this protein and induces the cleavage of this protein's C-terminal zinc finger domain. This protein also promotes the nuclear translocation of p120. Mutations in this gene cause nephronophthisis (NPHP), an autosomal recessive kidney disease characterized by tubular basement membrane disruption, interstitial lymphohistiocytic cell infiltration, and development of cysts at the corticomedullary border of the kidneys.[provided by RefSeq, Jan 2010]
PAM16 (HGNC:29679): (presequence translocase associated motor 16) This gene encodes a mitochondrial protein involved in granulocyte-macrophage colony-stimulating factor (GM-CSF) signaling. This protein also plays a role in the import of nuclear-encoded mitochondrial proteins into the mitochondrial matrix and may be important in reactive oxygen species (ROS) homeostasis. Mutations in this gene cause Megarbane-Dagher-Melike type spondylometaphyseal dysplasia, an early lethal skeletal dysplasia characterized by short stature, developmental delay and other skeletal abnormalities. [provided by RefSeq, May 2017]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.007631421).
BP6
?
Variant 16-4334870-G-A is Benign according to our data. Variant chr16-4334870-G-A is described in ClinVar as [Benign]. Clinvar id is 241705.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
?
High Homozygotes in GnomAdExome4 at 2 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GLIS2 | NM_032575.3 | c.415G>A | p.Gly139Arg | missense_variant | 4/7 | ENST00000433375.2 | |
GLIS2 | NM_001318918.2 | c.415G>A | p.Gly139Arg | missense_variant | 5/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GLIS2 | ENST00000433375.2 | c.415G>A | p.Gly139Arg | missense_variant | 4/7 | 1 | NM_032575.3 | P1 | |
GLIS2 | ENST00000262366.7 | c.415G>A | p.Gly139Arg | missense_variant | 5/8 | 2 | P1 | ||
PAM16 | ENST00000577031.5 | c.292-3096C>T | intron_variant | 4 |
Frequencies
GnomAD3 genomes ? AF: 0.00279 AC: 423AN: 151876Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000861 AC: 215AN: 249630Hom.: 0 AF XY: 0.000561 AC XY: 76AN XY: 135476
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GnomAD4 exome AF: 0.000359 AC: 524AN: 1460622Hom.: 2 Cov.: 32 AF XY: 0.000314 AC XY: 228AN XY: 726610
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GnomAD4 genome ? AF: 0.00281 AC: 427AN: 151994Hom.: 0 Cov.: 32 AF XY: 0.00253 AC XY: 188AN XY: 74298
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Nephronophthisis Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 18, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
P;P
Vest4
MutPred
Loss of glycosylation at S138 (P = 0.0461);Loss of glycosylation at S138 (P = 0.0461);
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
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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