15-22786677-AGCGGCGGCGGCGGCGGCGGCG-AGCG
Variant summary
Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP3BP6_ModerateBS2
The NM_144599.5(NIPA1):c.30_47delGGCGGCGGCGGCGGCGGC(p.Ala11_Ala16del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000308 in 1,071,498 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0000069 ( 0 hom., cov: 6)
Exomes 𝑓: 0.000035 ( 0 hom. )
Consequence
NIPA1
NM_144599.5 disruptive_inframe_deletion
NM_144599.5 disruptive_inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 1.48
Publications
11 publications found
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]
NIPA1 Gene-Disease associations (from GenCC):
- hereditary spastic paraplegia 6Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Benign. The variant received -7 ACMG points.
BP3
Nonframeshift variant in repetitive region in NM_144599.5
BP6
Variant 15-22786677-AGCGGCGGCGGCGGCGGCG-A is Benign according to our data. Variant chr15-22786677-AGCGGCGGCGGCGGCGGCG-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3632912.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAdExome4 at 32 AD gene.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| NIPA1 | NM_144599.5 | c.30_47delGGCGGCGGCGGCGGCGGC | p.Ala11_Ala16del | disruptive_inframe_deletion | Exon 1 of 5 | ENST00000337435.9 | NP_653200.2 | |
| NIPA1 | NM_001142275.1 | c.-48+438_-48+455delGGCGGCGGCGGCGGCGGC | intron_variant | Intron 1 of 4 | NP_001135747.1 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| NIPA1 | ENST00000337435.9 | c.30_47delGGCGGCGGCGGCGGCGGC | p.Ala11_Ala16del | disruptive_inframe_deletion | Exon 1 of 5 | 1 | NM_144599.5 | ENSP00000337452.4 |
Frequencies
GnomAD3 genomes 0.00000688 AC: 1AN: 145406Hom.: 0 Cov.: 6 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
145406
Hom.:
Cov.:
6
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.0000346 AC: 32AN: 926092Hom.: 0 AF XY: 0.0000406 AC XY: 18AN XY: 442826 show subpopulations
GnomAD4 exome
AF:
AC:
32
AN:
926092
Hom.:
AF XY:
AC XY:
18
AN XY:
442826
show subpopulations
African (AFR)
AF:
AC:
0
AN:
17460
American (AMR)
AF:
AC:
0
AN:
5856
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
8166
East Asian (EAS)
AF:
AC:
0
AN:
8916
South Asian (SAS)
AF:
AC:
0
AN:
21810
European-Finnish (FIN)
AF:
AC:
1
AN:
8024
Middle Eastern (MID)
AF:
AC:
0
AN:
2628
European-Non Finnish (NFE)
AF:
AC:
31
AN:
820600
Other (OTH)
AF:
AC:
0
AN:
32632
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.450
Heterozygous variant carriers
0
2
4
5
7
9
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
4
8
12
16
20
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome 0.00000688 AC: 1AN: 145406Hom.: 0 Cov.: 6 AF XY: 0.0000141 AC XY: 1AN XY: 70686 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
145406
Hom.:
Cov.:
6
AF XY:
AC XY:
1
AN XY:
70686
show subpopulations
African (AFR)
AF:
AC:
1
AN:
40094
American (AMR)
AF:
AC:
0
AN:
14774
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3384
East Asian (EAS)
AF:
AC:
0
AN:
4834
South Asian (SAS)
AF:
AC:
0
AN:
4704
European-Finnish (FIN)
AF:
AC:
0
AN:
8836
Middle Eastern (MID)
AF:
AC:
0
AN:
304
European-Non Finnish (NFE)
AF:
AC:
0
AN:
65568
Other (OTH)
AF:
AC:
0
AN:
2014
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Genome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
Hom.:
ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Hereditary spastic paraplegia 6 Benign:1
Oct 17, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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