Variant 15-22786671-TGCGGCA-T 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_26delAGCGGC(p.Ala8_Ala9del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000835 in 1,065,976 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00032 ( 0 hom., cov: 27)

Exomes 𝑓: 0.000047 ( 1 hom. )

Consequence

NIPA1
NM_144599.5 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B: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 Benign. Variant got -13 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_144599.5

BP6

Variant 15-22786671-TGCGGCA-T is Benign according to our data. Variant chr15-22786671-TGCGGCA-T is described in ClinVar as [Likely_benign]. Clinvar id is 948284.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 45 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NIPA1	NM_144599.5 link	c.21_26delAGCGGC	p.Ala8_Ala9del	disruptive_inframe_deletion	1/5	ENST00000337435.9	NP_653200.2	Q7RTP0-1
NIPA1	NM_001142275.1 link	c.-48+429_-48+434delAGCGGC		intron_variant			NP_001135747.1	Q7RTP0-2A0A024R344Q8TAY1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
NIPA1	ENST00000337435.9 link	c.21_26delAGCGGC	p.Ala8_Ala9del	disruptive_inframe_deletion	1/5	1	NM_144599.5	ENSP00000337452.4	Q7RTP0-1
NIPA1	ENST00000437912.6 link	c.-48+12364_-48+12369delAGCGGC		intron_variant		1		ENSP00000393962.2	Q7RTP0-2
NIPA1	ENST00000561183.5 link	c.-48+429_-48+434delAGCGGC		intron_variant		1		ENSP00000453722.1	Q7RTP0-2
NIPA1	ENST00000560069.5 link	n.31+429_31+434delAGCGGC		intron_variant		4

Frequencies

GnomAD3 genomes

AF:

0.000324

AC:

AN:

138958

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000732

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00160

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000517

GnomAD3 exomes

AF:

0.0000887

AC:

AN:

11276

Hom.:

AF XY:

0.000149

AC XY:

AN XY:

6724

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000213

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000475

AC:

AN:

926926

Hom.:

AF XY:

0.0000406

AC XY:

AN XY:

443670

show subpopulations

Gnomad4 AFR exome

AF:

0.000797

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000342

Gnomad4 SAS exome

AF:

0.0000883

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000269

Gnomad4 OTH exome

AF:

0.0000918

GnomAD4 genome

AF:

0.000324

AC:

AN:

139050

Hom.:

Cov.:

AF XY:

0.000326

AC XY:

AN XY:

67480

show subpopulations

Gnomad4 AFR

AF:

0.000962

Gnomad4 AMR

AF:

0.0000731

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00161

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000511

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

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

Sep 01, 2021

- -

Hereditary spastic paraplegia 6

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Apr 22, 2024

- -

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