rs11263683
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_144599.5(NIPA1):āc.441A>Gā(p.Thr147=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.728 in 1,611,202 control chromosomes in the GnomAD database, including 431,836 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.67 ( 35508 hom., cov: 32)
Exomes š: 0.73 ( 396328 hom. )
Consequence
NIPA1
NM_144599.5 synonymous
NM_144599.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -5.55
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 Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.91).
BP6
?
Variant 15-22820436-A-G is Benign according to our data. Variant chr15-22820436-A-G is described in ClinVar as [Benign]. Clinvar id is 129804.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-22820436-A-G is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=-5.55 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.838 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NIPA1 | NM_144599.5 | c.441A>G | p.Thr147= | synonymous_variant | 4/5 | ENST00000337435.9 | |
NIPA1 | NM_001142275.1 | c.216A>G | p.Thr72= | synonymous_variant | 4/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NIPA1 | ENST00000337435.9 | c.441A>G | p.Thr147= | synonymous_variant | 4/5 | 1 | NM_144599.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.671 AC: 101976AN: 151912Hom.: 35486 Cov.: 32
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GnomAD3 exomes AF: 0.745 AC: 187314AN: 251454Hom.: 71106 AF XY: 0.749 AC XY: 101781AN XY: 135902
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GnomAD4 exome AF: 0.734 AC: 1071301AN: 1459172Hom.: 396328 Cov.: 39 AF XY: 0.738 AC XY: 535601AN XY: 726056
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GnomAD4 genome ? AF: 0.671 AC: 102037AN: 152030Hom.: 35508 Cov.: 32 AF XY: 0.672 AC XY: 49963AN XY: 74318
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ClinVar
Significance: Benign
Submissions summary: Benign:10
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:5
Likely benign, no assertion criteria provided | clinical testing | Genetic Services Laboratory, University of Chicago | - | Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. - |
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 21, 2016 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Nov 22, 2019 | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Hereditary spastic paraplegia 6 Benign:4
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Sep 05, 2021 | - - |
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Hereditary spastic paraplegia Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Dec 12, 2016 | - - |
Computational scores
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Name
Calibrated prediction
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Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at