Variant 15-22786674-GGCA-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_144599.5(NIPA1):c.21_23del(p.Ala16del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000216 in 1,074,954 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. A7A) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00025 ( 0 hom., cov: 27)

Exomes 𝑓: 0.00021 ( 0 hom. )

Consequence

NIPA1
NM_144599.5 inframe_deletion

Scores

Not classified

Clinical Significance

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

Conservation

PhyloP100: 1.62

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 15-22786674-GGCA-G is Benign according to our data. Variant chr15-22786674-GGCA-G is described in ClinVar as [Likely_benign]. Clinvar id is 695853.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 34 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NIPA1	NM_144599.5 linkuse as main transcript	c.21_23del	p.Ala16del	inframe_deletion	1/5	ENST00000337435.9
NIPA1	NM_001142275.1 linkuse as main transcript	c.-48+429_-48+431del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NIPA1	ENST00000337435.9 linkuse as main transcript	c.21_23del	p.Ala16del	inframe_deletion	1/5	1	NM_144599.5	P1	Q7RTP0-1
NIPA1	ENST00000437912.6 linkuse as main transcript	c.-48+12364_-48+12366del		intron_variant		1			Q7RTP0-2
NIPA1	ENST00000561183.5 linkuse as main transcript	c.-48+429_-48+431del		intron_variant		1			Q7RTP0-2
NIPA1	ENST00000560069.5 linkuse as main transcript	n.31+429_31+431del		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes

AF:

0.000250

AC:

AN:

135802

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000277

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000150

Gnomad ASJ

AF:

0.000308

Gnomad EAS

AF:

0.000245

Gnomad SAS

AF:

0.00333

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000221

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000369

AC:

AN:

10834

Hom.:

AF XY:

0.000311

AC XY:

AN XY:

6422

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00196

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000211

AC:

198

AN:

939078

Hom.:

AF XY:

0.000218

AC XY:

AN XY:

449476

show subpopulations

Gnomad4 AFR exome

AF:

0.000113

Gnomad4 AMR exome

AF:

0.000147

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000110

Gnomad4 SAS exome

AF:

0.00185

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000175

Gnomad4 OTH exome

AF:

0.000211

GnomAD4 genome

AF:

0.000250

AC:

AN:

135876

Hom.:

Cov.:

AF XY:

0.000288

AC XY:

AN XY:

65866

show subpopulations

Gnomad4 AFR

AF:

0.0000277

Gnomad4 AMR

AF:

0.000150

Gnomad4 ASJ

AF:

0.000308

Gnomad4 EAS

AF:

0.000245

Gnomad4 SAS

AF:

0.00334

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000221

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000843

Hom.:

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Hereditary spastic paraplegia

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Mar 01, 2018

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 05, 2022

- -

Hereditary spastic paraplegia 6

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Apr 07, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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