Variant 15-22786671-TGCGGCAGCGGCGGCGGCG-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP3BS2

The NM_144599.5(NIPA1):c.21_38del(p.Ala11_Ala16del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000178 in 1,065,912 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.000065 ( 0 hom., cov: 6)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

NIPA1
NM_144599.5 inframe_deletion

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 2.80

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 -5 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_144599.5

BS2

High AC in GnomAd at 9 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NIPA1	NM_144599.5 linkuse as main transcript	c.21_38del	p.Ala11_Ala16del	inframe_deletion	1/5	ENST00000337435.9
NIPA1	NM_001142275.1 linkuse as main transcript	c.-48+429_-48+446del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NIPA1	ENST00000337435.9 linkuse as main transcript	c.21_38del	p.Ala11_Ala16del	inframe_deletion	1/5	1	NM_144599.5	P1	Q7RTP0-1
NIPA1	ENST00000437912.6 linkuse as main transcript	c.-48+12364_-48+12381del		intron_variant		1			Q7RTP0-2
NIPA1	ENST00000561183.5 linkuse as main transcript	c.-48+429_-48+446del		intron_variant		1			Q7RTP0-2
NIPA1	ENST00000560069.5 linkuse as main transcript	n.31+429_31+446del		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes

AF:

0.0000648

AC:

AN:

138958

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000268

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000125

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000108

AC:

AN:

926954

Hom.:

AF XY:

0.0000135

AC XY:

AN XY:

443684

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000120

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000110

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000648

AC:

AN:

138958

Hom.:

Cov.:

AF XY:

0.0000891

AC XY:

AN XY:

67372

show subpopulations

Gnomad4 AFR

AF:

0.0000268

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000125

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000227

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Hereditary spastic paraplegia 6

Uncertain:2

Uncertain significance, criteria provided, single submitter	clinical testing	Invitae	Jan 21, 2023	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. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant has not been reported in the literature in individuals affected with NIPA1-related conditions. 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, c.21_38del, results in the deletion of 6 amino acid(s) of the NIPA1 protein (p.Ala11_Ala16del), but otherwise preserves the integrity of the reading frame. -
Uncertain significance, criteria provided, single submitter	clinical testing	Revvity Omics, Revvity	Mar 04, 2021	- -

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