15-22786677-AGCGGCGGCGGCGGCGGCGGCG-AGCGGCGGCGGCG

Variant names:

• chr15-22786677-AGCGGCGGCG-A
• rs531550505
• NM_144599.5:c.39_47delGGCGGCGGC

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP3 BP6_Very_Strong BS2

The NM_144599.5(NIPA1):​c.39_47delGGCGGCGGC​(p.Ala14_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 0.00171 in 1,071,494 control chromosomes in the GnomAD database, including 8 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0014 (0 hom., cov: 6)
  • Exomes 𝑓: 0.0018 (8 hom.)
• Consequence: NIPA1 NM_144599.5 disruptive_inframe_deletion
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• 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 6

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

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_144599.5
• BP6: Variant 15-22786677-AGCGGCGGCG-A is Benign according to our data. Variant chr15-22786677-AGCGGCGGCG-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 241881.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 201 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NIPA1	NM_144599.5	MANE Select	c.39_47delGGCGGCGGC	p.Ala14_Ala16del	disruptive_inframe_deletion	Exon 1 of 5	NP_653200.2
	NIPA1	NM_001142275.1		c.-48+447_-48+455delGGCGGCGGC		intron	N/A	NP_001135747.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NIPA1	ENST00000337435.9	TSL:1 MANE Select	c.39_47delGGCGGCGGC	p.Ala14_Ala16del	disruptive_inframe_deletion	Exon 1 of 5	ENSP00000337452.4
	NIPA1	ENST00000437912.6	TSL:1	c.-48+12382_-48+12390delGGCGGCGGC		intron	N/A	ENSP00000393962.2
	NIPA1	ENST00000561183.5	TSL:1	c.-48+447_-48+455delGGCGGCGGC		intron	N/A	ENSP00000453722.1

Frequencies

GnomAD3 genomes AF: 0.00138 AC: 201 AN: 145406 Hom.: 0 Cov.: 6

Gnomad AFR AF: 0.000399

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000406

Gnomad ASJ AF: 0.00650

Gnomad EAS AF: 0.00476

Gnomad SAS AF: 0.000425

Gnomad FIN AF: 0.00306

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00156

Gnomad OTH AF: 0.00149

GnomAD2 exomes AF: 0.000743 AC: 15 AN: 20176 AF XY: 0.000948

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000453

Gnomad ASJ exome AF: 0.00171

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000550

Gnomad NFE exome AF: 0.000682

Gnomad OTH exome AF: 0.00163

GnomAD4 exome AF: 0.00177 AC: 1635 AN: 926006 Hom.: 8 AF XY: 0.00182 AC XY: 806 AN XY: 442788

African (AFR) AF: 0.000745 AC: 13 AN: 17460

American (AMR) AF: 0.000342 AC: 2 AN: 5846

Ashkenazi Jewish (ASJ) AF: 0.00453 AC: 37 AN: 8164

East Asian (EAS) AF: 0.0104 AC: 93 AN: 8912

South Asian (SAS) AF: 0.000871 AC: 19 AN: 21804

European-Finnish (FIN) AF: 0.00424 AC: 34 AN: 8020

Middle Eastern (MID) AF: 0.00266 AC: 7 AN: 2628

European-Non Finnish (NFE) AF: 0.00168 AC: 1376 AN: 820550

Other (OTH) AF: 0.00166 AC: 54 AN: 32622

GnomAD4 genome AF: 0.00138 AC: 201 AN: 145488 Hom.: 0 Cov.: 6 AF XY: 0.00130 AC XY: 92 AN XY: 70786

African (AFR) AF: 0.000398 AC: 16 AN: 40200

American (AMR) AF: 0.000406 AC: 6 AN: 14790

Ashkenazi Jewish (ASJ) AF: 0.00650 AC: 22 AN: 3384

East Asian (EAS) AF: 0.00478 AC: 23 AN: 4816

South Asian (SAS) AF: 0.000426 AC: 2 AN: 4698

European-Finnish (FIN) AF: 0.00306 AC: 27 AN: 8836

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 282

European-Non Finnish (NFE) AF: 0.00156 AC: 102 AN: 65558

Other (OTH) AF: 0.00148 AC: 3 AN: 2030

Alfa AF: 0.000769 Hom.: 108

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Mar 23, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 24866401)

May 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

NIPA1: BS1

Hereditary spastic paraplegia 6 Benign:1

Dec 31, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Other links and lift over

dbSNP: rs531550505; hg19: chr15-23086391;