Variant 15-22786663-ACTGCAG-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM4BS2

The NM_144599.5(NIPA1):c.12_17del(p.Ala15_Ala16del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.0000246 in 1,058,648 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000062 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

NIPA1
NM_144599.5 inframe_deletion

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.81

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 -2 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_144599.5.

BS2

High AC in GnomAd4 at 9 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NIPA1	NM_144599.5 linkuse as main transcript	c.12_17del	p.Ala15_Ala16del	inframe_deletion	1/5	ENST00000337435.9
NIPA1	NM_001142275.1 linkuse as main transcript	c.-48+420_-48+425del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NIPA1	ENST00000337435.9 linkuse as main transcript	c.12_17del	p.Ala15_Ala16del	inframe_deletion	1/5	1	NM_144599.5	P1	Q7RTP0-1
NIPA1	ENST00000437912.6 linkuse as main transcript	c.-48+12355_-48+12360del		intron_variant		1			Q7RTP0-2
NIPA1	ENST00000561183.5 linkuse as main transcript	c.-48+420_-48+425del		intron_variant		1			Q7RTP0-2
NIPA1	ENST00000560069.5 linkuse as main transcript	n.31+420_31+425del		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes

AF:

0.0000625

AC:

AN:

143924

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000510

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000138

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000215

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000609

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000186

AC:

AN:

914624

Hom.:

AF XY:

0.0000206

AC XY:

AN XY:

437724

show subpopulations

Gnomad4 AFR exome

AF:

0.000116

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000173

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000625

AC:

AN:

144024

Hom.:

Cov.:

AF XY:

0.0000999

AC XY:

AN XY:

70044

show subpopulations

Gnomad4 AFR

AF:

0.0000508

Gnomad4 AMR

AF:

0.000138

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000216

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000609

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Hereditary spastic paraplegia 6

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Sep 26, 2023

This variant, c.12_17del, results in the deletion of 2 amino acid(s) of the NIPA1 protein (p.Ala15_Ala16del), 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. This variant has been observed in at least one individual who was not affected with NIPA1-related conditions (Invitae). ClinVar contains an entry for this variant (Variation ID: 639570). 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. -

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