rs7166056

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
NIPA1	NM_144599.5	c.179-10343C>G		intron_variant		ENST00000337435.9	NP_653200.2
NIPA1	NM_001142275.1	c.-47-10343C>G		intron_variant			NP_001135747.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NIPA1	ENST00000337435.9	c.179-10343C>G		intron_variant		1	NM_144599.5	ENSP00000337452	P1

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

Gnomad4 AFR AF: 0.176

Gnomad4 AMR AF: 0.0287

Gnomad4 ASJ AF: 0.0190

Gnomad4 EAS AF: 0.134

Gnomad4 SAS AF: 0.0458

Gnomad4 FIN AF: 0.0105

Gnomad4 NFE AF: 0.0172

Gnomad4 OTH AF: 0.0617

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

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

Other links and lift over

dbSNP: rs7166056; hg19: chr15-23072662;