Variant 15-22786677-A-AGCGGCGGCG details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -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

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 Likely_benign. Variant got -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 id is 533362.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=2, Likely_benign=2}.

BS2

High AC in GnomAd4 at 30 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NIPA1	NM_144599.5 link	c.39_47dupGGCGGCGGC	p.Ala14_Ala16dup	disruptive_inframe_insertion	1/5	ENST00000337435.9	NP_653200.2	Q7RTP0-1
NIPA1	NM_001142275.1 link	c.-48+447_-48+455dupGGCGGCGGC		intron_variant			NP_001135747.1	Q7RTP0-2A0A024R344Q8TAY1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
NIPA1	ENST00000337435.9 link	c.39_47dupGGCGGCGGC	p.Ala14_Ala16dup	disruptive_inframe_insertion	1/5	1	NM_144599.5	ENSP00000337452.4	Q7RTP0-1
NIPA1	ENST00000437912.6 link	c.-48+12382_-48+12390dupGGCGGCGGC		intron_variant		1		ENSP00000393962.2	Q7RTP0-2
NIPA1	ENST00000561183.5 link	c.-48+447_-48+455dupGGCGGCGGC		intron_variant		1		ENSP00000453722.1	Q7RTP0-2
NIPA1	ENST00000560069.5 link	n.31+447_31+455dupGGCGGCGGC		intron_variant		4

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

Gnomad4 AFR exome

AF:

0.000172

Gnomad4 AMR exome

AF:

0.000342

Gnomad4 ASJ exome

AF:

0.000367

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000138

Gnomad4 FIN exome

AF:

0.000125

Gnomad4 NFE exome

AF:

0.000225

Gnomad4 OTH exome

AF:

0.000153

GnomAD4 genome

AF:

0.000206

AC:

AN:

145488

Hom.:

Cov.:

AF XY:

0.000170

AC XY:

AN XY:

70786

show subpopulations

Gnomad4 AFR

AF:

0.000149

Gnomad4 AMR

AF:

0.000338

Gnomad4 ASJ

AF:

0.000296

Gnomad4 EAS

AF:

0.000415

Gnomad4 SAS

AF:

0.000851

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000183

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:2Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Hereditary spastic paraplegia

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Feb 01, 2020

- -

Hereditary spastic paraplegia 6

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 14, 2025

This variant, c.39_47dup, results in the insertion of 3 amino acid(s) of the NIPA1 protein (p.Ala14_Ala16dup), but otherwise preserves the integrity of the reading frame. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with NIPA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 533362). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Athena Diagnostics

Jan 19, 2024

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 07, 2020

- -

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.

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