Genetic Variant NIPA1:p.Ala14_Ala16del (chr15-22786677-AGCGGCGGCG-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP3BP6_Very_StrongBS2

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

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.48

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 [Likely_benign]. Clinvar id is 241881.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 201 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NIPA1	NM_144599.5 link	c.39_47delGGCGGCGGC	p.Ala14_Ala16del	disruptive_inframe_deletion	Exon 1 of 5	ENST00000337435.9	NP_653200.2	Q7RTP0-1
NIPA1	NM_001142275.1 link	c.-48+447_-48+455delGGCGGCGGC		intron_variant	Intron 1 of 4		NP_001135747.1	Q7RTP0-2A0A024R344Q8TAY1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NIPA1	ENST00000337435.9 link	c.39_47delGGCGGCGGC	p.Ala14_Ala16del	disruptive_inframe_deletion	Exon 1 of 5	1	NM_144599.5	ENSP00000337452.4		Q7RTP0-1

Frequencies

GnomAD3 genomes

AF:

0.00138

AC:

201

AN:

145406

Hom.:

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.000743

AC:

AN:

20176

Hom.:

AF XY:

0.000948

AC XY:

AN XY:

12652

show subpopulations

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 SAS exome

AF:

0.000638

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.:

AF XY:

0.00182

AC XY:

806

AN XY:

442788

show subpopulations

Gnomad4 AFR exome

AF:

0.000745

Gnomad4 AMR exome

AF:

0.000342

Gnomad4 ASJ exome

AF:

0.00453

Gnomad4 EAS exome

AF:

0.0104

Gnomad4 SAS exome

AF:

0.000871

Gnomad4 FIN exome

AF:

0.00424

Gnomad4 NFE exome

AF:

0.00168

Gnomad4 OTH exome

AF:

0.00166

GnomAD4 genome

AF:

0.00138

AC:

201

AN:

145488

Hom.:

Cov.:

AF XY:

0.00130

AC XY:

AN XY:

70786

show subpopulations

Gnomad4 AFR

AF:

0.000398

Gnomad4 AMR

AF:

0.000406

Gnomad4 ASJ

AF:

0.00650

Gnomad4 EAS

AF:

0.00478

Gnomad4 SAS

AF:

0.000426

Gnomad4 FIN

AF:

0.00306

Gnomad4 NFE

AF:

0.00156

Gnomad4 OTH

AF:

0.00148

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Mar 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

NIPA1: BS1, BS2 -

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) -

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 v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

15-22786677-AGCGGCGGCGGCGGCGGCGGCG-AGCGGCGGCGGCG

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over