rs8027341

Variant names:

• chr15-22819856-A-G
• rs8027341
• NM_144599.5:c.318-457A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_144599.5(NIPA1):​c.318-457A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 152,020 control chromosomes in the GnomAD database, including 6,646 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.29 (6646 hom., cov: 33)
• Consequence: NIPA1 NM_144599.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.896
• Publications: 5 publications found

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 Gene-Disease associations (from GenCC):

• hereditary spastic paraplegia 6

  Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.319 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NIPA1	NM_144599.5	c.318-457A>G		intron_variant	Intron 3 of 4	ENST00000337435.9	NP_653200.2
NIPA1	NM_001142275.1	c.93-457A>G		intron_variant	Intron 3 of 4		NP_001135747.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NIPA1	ENST00000337435.9	c.318-457A>G		intron_variant	Intron 3 of 4	1	NM_144599.5	ENSP00000337452.4

Frequencies

GnomAD3 genomes AF: 0.291 AC: 44234 AN: 151902 Hom.: 6640 Cov.: 33

Gnomad AFR AF: 0.272

Gnomad AMI AF: 0.453

Gnomad AMR AF: 0.238

Gnomad ASJ AF: 0.357

Gnomad EAS AF: 0.213

Gnomad SAS AF: 0.298

Gnomad FIN AF: 0.242

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.323

Gnomad OTH AF: 0.290

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.291 AC: 44258 AN: 152020 Hom.: 6646 Cov.: 33 AF XY: 0.286 AC XY: 21290 AN XY: 74316

African (AFR) AF: 0.271 AC: 11249 AN: 41444

American (AMR) AF: 0.237 AC: 3628 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.357 AC: 1238 AN: 3470

East Asian (EAS) AF: 0.212 AC: 1098 AN: 5176

South Asian (SAS) AF: 0.299 AC: 1442 AN: 4822

European-Finnish (FIN) AF: 0.242 AC: 2551 AN: 10562

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.323 AC: 21936 AN: 67954

Other (OTH) AF: 0.291 AC: 614 AN: 2108

Alfa AF: 0.302 Hom.: 1282

Bravo AF: 0.289

Asia WGS AF: 0.254 AC: 884 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.40
DANN	Benign	0.55
PhyloP100		-0.90

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

Other links and lift over

dbSNP: rs8027341; hg19: chr15-23053212;