16-4333330-C-G
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate
The NM_032575.3(GLIS2):c.173-17C>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000186 in 1,612,488 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 Likely benign (★).
Frequency
Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000075 ( 0 hom. )
Consequence
GLIS2
NM_032575.3 splice_polypyrimidine_tract, intron
NM_032575.3 splice_polypyrimidine_tract, intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.48
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 Likely_benign. Variant got -4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.91).
BP6
Variant 16-4333330-C-G is Benign according to our data. Variant chr16-4333330-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2186069.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GLIS2 | NM_032575.3 | c.173-17C>G | splice_polypyrimidine_tract_variant, intron_variant | ENST00000433375.2 | |||
GLIS2 | NM_001318918.2 | c.173-17C>G | splice_polypyrimidine_tract_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GLIS2 | ENST00000433375.2 | c.173-17C>G | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_032575.3 | P1 | |||
GLIS2 | ENST00000262366.7 | c.173-17C>G | splice_polypyrimidine_tract_variant, intron_variant | 2 | P1 | ||||
PAM16 | ENST00000577031.5 | c.292-1556G>C | intron_variant | 4 |
Frequencies
GnomAD3 genomes AF: 0.000125 AC: 19AN: 152200Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000321 AC: 8AN: 249582Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135444
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GnomAD4 exome AF: 0.00000753 AC: 11AN: 1460288Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3AN XY: 726492
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GnomAD4 genome AF: 0.000125 AC: 19AN: 152200Hom.: 0 Cov.: 32 AF XY: 0.000108 AC XY: 8AN XY: 74352
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Nephronophthisis Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | May 09, 2022 | - - |
Computational scores
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Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at