rs7166056

Variant names:

• chr15-22800406-C-G
• rs7166056
• NM_144599.5:c.179-10343C>G

Your query was ambiguous. Multiple possible variants found:

• chr15-22800406-C-G
• chr15-22800406-C-T

Variant summary

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

The NM_144599.5(NIPA1):​c.179-10343C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0669 in 152,140 control chromosomes in the GnomAD database, including 761 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 0.067 (761 hom., cov: 31)
• Consequence: NIPA1 NM_144599.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.720
• Publications: 0 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.173 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NIPA1	NM_144599.5	c.179-10343C>G		intron_variant	Intron 1 of 4	ENST00000337435.9	NP_653200.2
NIPA1	NM_001142275.1	c.-47-10343C>G		intron_variant	Intron 1 of 4		NP_001135747.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NIPA1	ENST00000337435.9	c.179-10343C>G		intron_variant	Intron 1 of 4	1	NM_144599.5	ENSP00000337452.4

Frequencies

GnomAD3 genomes AF: 0.0668 AC: 10160 AN: 152022 Hom.: 760 Cov.: 31

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0287

Gnomad ASJ AF: 0.0190

Gnomad EAS AF: 0.134

Gnomad SAS AF: 0.0459

Gnomad FIN AF: 0.0105

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0172

Gnomad OTH AF: 0.0609

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

GnomAD4 genome AF: 0.0669 AC: 10173 AN: 152140 Hom.: 761 Cov.: 31 AF XY: 0.0649 AC XY: 4829 AN XY: 74390

African (AFR) AF: 0.176 AC: 7321 AN: 41482

American (AMR) AF: 0.0287 AC: 438 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.0190 AC: 66 AN: 3466

East Asian (EAS) AF: 0.134 AC: 693 AN: 5188

South Asian (SAS) AF: 0.0458 AC: 221 AN: 4830

European-Finnish (FIN) AF: 0.0105 AC: 111 AN: 10588

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0172 AC: 1168 AN: 68010

Other (OTH) AF: 0.0617 AC: 130 AN: 2108

Alfa AF: 0.0122 Hom.: 14

Bravo AF: 0.0726

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.95
DANN	Benign	0.40
PhyloP100		-0.72

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: rs7166056; hg19: chr15-23072662;