Genetic Variant NIPA1:p.Ala14_Ala16dup (chr15-22786677-A-AGCGGCGGCG) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP3BP6BS2

The NM_144599.5(NIPA1):c.39_47dupGGCGGCGGC(p.Ala14_Ala16dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00021 ( 0 hom., cov: 6)

Exomes 𝑓: 0.00022 ( 0 hom. )

Consequence

NIPA1
NM_144599.5 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:2

Conservation

PhyloP100: 1.48

Publications

11 publications found

Variant links:

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 6
Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics

NIPA1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_144599.5

BP6

Variant 15-22786677-A-AGCGGCGGCG is Benign according to our data. Variant chr15-22786677-A-AGCGGCGGCG is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 533362.

BS2

High AC in GnomAd4 at 30 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144599.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NIPA1	NM_144599.5	MANE Select	c.39_47dupGGCGGCGGC	p.Ala14_Ala16dup	disruptive_inframe_insertion	Exon 1 of 5	NP_653200.2
	NIPA1	NM_001142275.1		c.-48+447_-48+455dupGGCGGCGGC		intron	N/A	NP_001135747.1	Q8TAY1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NIPA1	ENST00000337435.9	TSL:1 MANE Select	c.39_47dupGGCGGCGGC	p.Ala14_Ala16dup	disruptive_inframe_insertion	Exon 1 of 5	ENSP00000337452.4	Q7RTP0-1
NIPA1	ENST00000437912.6	TSL:1	c.-48+12382_-48+12390dupGGCGGCGGC		intron	N/A	ENSP00000393962.2	Q7RTP0-2
NIPA1	ENST00000561183.5	TSL:1	c.-48+447_-48+455dupGGCGGCGGC		intron	N/A	ENSP00000453722.1	Q7RTP0-2

Frequencies

GnomAD3 genomes

AF:

0.000206

AC:

AN:

145406

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000150

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000338

Gnomad ASJ

AF:

0.000296

Gnomad EAS

AF:

0.000414

Gnomad SAS

AF:

0.000850

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000183

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000218

AC:

202

AN:

926066

Hom.:

Cov.:

AF XY:

0.000228

AC XY:

101

AN XY:

442810

show subpopulations

African (AFR)

AF:

0.000172

AC:

AN:

17460

American (AMR)

AF:

0.000342

AC:

AN:

5856

Ashkenazi Jewish (ASJ)

AF:

0.000367

AC:

AN:

8166

East Asian (EAS)

AF:

0.00

AC:

AN:

8916

South Asian (SAS)

AF:

0.000138

AC:

AN:

21810

European-Finnish (FIN)

AF:

0.000125

AC:

AN:

8024

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2626

European-Non Finnish (NFE)

AF:

0.000225

AC:

185

AN:

820578

Other (OTH)

AF:

0.000153

AC:

AN:

32630

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.400

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

AF:

0.000206

AC:

AN:

145488

Hom.:

Cov.:

AF XY:

0.000170

AC XY:

AN XY:

70786

show subpopulations

African (AFR)

AF:

0.000149

AC:

AN:

40200

American (AMR)

AF:

0.000338

AC:

AN:

14790

Ashkenazi Jewish (ASJ)

AF:

0.000296

AC:

AN:

3384

East Asian (EAS)

AF:

0.000415

AC:

AN:

4816

South Asian (SAS)

AF:

0.000851

AC:

AN:

4698

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8836

Middle Eastern (MID)

AF:

0.00

AC:

AN:

282

European-Non Finnish (NFE)

AF:

0.000183

AC:

AN:

65558

Other (OTH)

AF:

0.00

AC:

AN:

2030

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

108

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

Hereditary spastic paraplegia (1)

Hereditary spastic paraplegia 6 (1)

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.5

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

15-22786677-AGCGGCGGCGGCGGCGGCGGCG-AGCGGCGGCGGCGGCGGCGGCGGCGGCGGCG

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over