rs7168367

Variant names:

• chr15-22806332-G-A
• rs7168367
• NM_144599.5:c.179-4417G>A

Variant summary

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

The NM_144599.5(NIPA1):​c.179-4417G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.326 in 152,124 control chromosomes in the GnomAD database, including 13,611 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 0.33 (13611 hom., cov: 33)
• Consequence: NIPA1 NM_144599.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.488
• Publications: 6 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: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.731 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144599.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NIPA1	NM_144599.5	MANE Select	c.179-4417G>A		intron	N/A	NP_653200.2
	NIPA1	NM_001142275.1		c.-47-4417G>A		intron	N/A	NP_001135747.1	Q8TAY1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NIPA1	ENST00000337435.9	TSL:1 MANE Select	c.179-4417G>A		intron	N/A	ENSP00000337452.4	Q7RTP0-1
	NIPA1	ENST00000437912.6	TSL:1	c.-47-4417G>A		intron	N/A	ENSP00000393962.2	Q7RTP0-2
	NIPA1	ENST00000561183.5	TSL:1	c.-47-4417G>A		intron	N/A	ENSP00000453722.1	Q7RTP0-2

Frequencies

GnomAD3 genomes AF: 0.326 AC: 49516 AN: 152006 Hom.: 13579 Cov.: 33

Gnomad AFR AF: 0.738

Gnomad AMI AF: 0.0725

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.179

Gnomad EAS AF: 0.578

Gnomad SAS AF: 0.205

Gnomad FIN AF: 0.135

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.139

Gnomad OTH AF: 0.279

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

GnomAD4 genome AF: 0.326 AC: 49591 AN: 152124 Hom.: 13611 Cov.: 33 AF XY: 0.322 AC XY: 23905 AN XY: 74354

African (AFR) AF: 0.738 AC: 30624 AN: 41508

American (AMR) AF: 0.183 AC: 2790 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.179 AC: 621 AN: 3468

East Asian (EAS) AF: 0.577 AC: 2983 AN: 5168

South Asian (SAS) AF: 0.204 AC: 982 AN: 4816

European-Finnish (FIN) AF: 0.135 AC: 1427 AN: 10584

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.139 AC: 9471 AN: 67984

Other (OTH) AF: 0.278 AC: 587 AN: 2114

Alfa AF: 0.195 Hom.: 20554

Bravo AF: 0.349

Asia WGS AF: 0.386 AC: 1341 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.2
DANN	Benign	0.44
PhyloP100		0.49

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: rs7168367; hg19: chr15-23066736;