15-22786677-A-G
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Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2
The NM_144599.5(NIPA1):āc.21A>Gā(p.Ala7=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000324 in 1,071,576 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: š 0.00027 ( 0 hom., cov: 27)
Exomes š: 0.00033 ( 0 hom. )
Consequence
NIPA1
NM_144599.5 synonymous
NM_144599.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.16
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 -10 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.78).
BP6
Variant 15-22786677-A-G is Benign according to our data. Variant chr15-22786677-A-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 380931.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=3, Uncertain_significance=1}.
BP7
Synonymous conserved (PhyloP=-1.15 with no splicing effect.
BS2
High AC in GnomAd4 at 39 AD gene.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| NIPA1 | NM_144599.5 | c.21A>G | p.Ala7= | synonymous_variant | 1/5 | ENST00000337435.9 | NP_653200.2 | |
| NIPA1 | NM_001142275.1 | c.-48+429A>G | intron_variant | NP_001135747.1 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| NIPA1 | ENST00000337435.9 | c.21A>G | p.Ala7= | synonymous_variant | 1/5 | 1 | NM_144599.5 | ENSP00000337452 | P1 | |
| NIPA1 | ENST00000437912.6 | c.-48+12364A>G | intron_variant | 1 | ENSP00000393962 | |||||
| NIPA1 | ENST00000561183.5 | c.-48+429A>G | intron_variant | 1 | ENSP00000453722 | |||||
| NIPA1 | ENST00000560069.5 | n.31+429A>G | intron_variant, non_coding_transcript_variant | 4 |
Frequencies
GnomAD3 genomes 0.000268 AC: 39AN: 145408Hom.: 0 Cov.: 27
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GnomAD3 exomes AF: 0.000639 AC: 7AN: 10952Hom.: 0 AF XY: 0.000931 AC XY: 6AN XY: 6444
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GnomAD4 exome AF: 0.000333 AC: 308AN: 926086Hom.: 0 Cov.: 20 AF XY: 0.000296 AC XY: 131AN XY: 442822
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GnomAD4 genome 0.000268 AC: 39AN: 145490Hom.: 0 Cov.: 27 AF XY: 0.000268 AC XY: 19AN XY: 70786
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:3
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Hereditary spastic paraplegia 6 Uncertain:1Benign:1
| Uncertain significance, 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
| Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 15, 2023 | - - |
Hereditary spastic paraplegia Benign:1
| Likely benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Dec 01, 2018 | - - |
not provided Benign:1
| Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 09, 2021 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at