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

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP3BP6BS2

The ENST00000337435.9(NIPA1):c.36_47del(p.Ala13_Ala16del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000136 in 1,071,552 control chromosomes in the GnomAD database, including 4 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. A8A) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 6)

Exomes 𝑓: 0.00014 ( 4 hom. )

Consequence

NIPA1
ENST00000337435.9 inframe_deletion

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

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 ENST00000337435.9

BP6

Variant 15-22786677-AGCGGCGGCGGCG-A is Benign according to our data. Variant chr15-22786677-AGCGGCGGCGGCG-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 872110.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.

BS2

High AC in GnomAd4 at 17 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NIPA1	NM_144599.5 linkuse as main transcript	c.36_47del	p.Ala13_Ala16del	inframe_deletion	1/5	ENST00000337435.9	NP_653200.2
NIPA1	NM_001142275.1 linkuse as main transcript	c.-48+444_-48+455del		intron_variant			NP_001135747.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NIPA1	ENST00000337435.9 linkuse as main transcript	c.36_47del	p.Ala13_Ala16del	inframe_deletion	1/5	1	NM_144599.5	ENSP00000337452	P1	Q7RTP0-1
NIPA1	ENST00000437912.6 linkuse as main transcript	c.-48+12379_-48+12390del		intron_variant		1		ENSP00000393962		Q7RTP0-2
NIPA1	ENST00000561183.5 linkuse as main transcript	c.-48+444_-48+455del		intron_variant		1		ENSP00000453722		Q7RTP0-2
NIPA1	ENST00000560069.5 linkuse as main transcript	n.31+444_31+455del		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes

AF:

0.000117

AC:

AN:

145406

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000224

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000425

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000915

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000139

AC:

129

AN:

926064

Hom.:

AF XY:

0.000149

AC XY:

AN XY:

442810

show subpopulations

Gnomad4 AFR exome

AF:

0.000115

Gnomad4 AMR exome

AF:

0.000171

Gnomad4 ASJ exome

AF:

0.000122

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000367

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000135

Gnomad4 OTH exome

AF:

0.000184

GnomAD4 genome

AF:

0.000117

AC:

AN:

145488

Hom.:

Cov.:

AF XY:

0.0000848

AC XY:

AN XY:

70786

show subpopulations

Gnomad4 AFR

AF:

0.000224

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000426

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000915

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Hereditary spastic paraplegia 6

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Apr 09, 2021

This variant has not been reported in the literature in individuals with NIPA1-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This variant, c.36_47del, results in the deletion of 4 amino acid(s) of the NIPA1 protein (p.Ala13_Ala16del), but otherwise preserves the integrity of the reading frame. 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 provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Oct 01, 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