rs1370367415
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP7
The NM_144599.5(NIPA1):c.99C>T(p.Gly33=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000258 in 1,162,818 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: 29)
Exomes 𝑓: 0.0000026 ( 0 hom. )
Consequence
NIPA1
NM_144599.5 synonymous
NM_144599.5 synonymous
Scores
1
1
Clinical Significance
Conservation
PhyloP100: 1.83
Genes affected
NIPA1 (HGNC:17043): (NIPA magnesium transporter 1) This gene encodes a magnesium transporter that associates with early endosomes and the cell surface in a variety of neuronal and epithelial cells. This protein may play a role in nervous system development and maintenance. Multiple transcript variants encoding different isoforms have been found for this gene. Mutations in this gene have been associated with autosomal dominant spastic paraplegia 6. [provided by RefSeq, Nov 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.42).
BP7
?
Synonymous conserved (PhyloP=1.83 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NIPA1 | NM_144599.5 | c.99C>T | p.Gly33= | synonymous_variant | 1/5 | ENST00000337435.9 | |
NIPA1 | NM_001142275.1 | c.-48+507C>T | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NIPA1 | ENST00000337435.9 | c.99C>T | p.Gly33= | synonymous_variant | 1/5 | 1 | NM_144599.5 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 29
GnomAD3 genomes
?
Cov.:
29
GnomAD4 exome AF: 0.00000258 AC: 3AN: 1162818Hom.: 0 Cov.: 32 AF XY: 0.00000521 AC XY: 3AN XY: 576098
GnomAD4 exome
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3
AN:
1162818
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32
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3
AN XY:
576098
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GnomAD4 genome ? Cov.: 29
GnomAD4 genome
?
Cov.:
29
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Hereditary spastic paraplegia 6 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 02, 2021 | The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. ClinVar contains an entry for this variant (Variation ID: 464775). This variant has not been reported in the literature in individuals affected with NIPA1-related conditions. This sequence change affects codon 33 of the NIPA1 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the NIPA1 protein. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
RBP_binding_hub_radar
RBP_regulation_power_radar
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