rs1356799862

Positions:

• chr15-22812235-C-A
• chr15-22812235-C-G
• chr15-22812235-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_144599.5(NIPA1):​c.299C>A​(p.Ala100Asp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A100V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: NIPA1 NM_144599.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.89

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 Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.904

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NIPA1	NM_144599.5	c.299C>A	p.Ala100Asp	missense_variant	3/5	ENST00000337435.9
NIPA1	NM_001142275.1	c.74C>A	p.Ala25Asp	missense_variant	3/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NIPA1	ENST00000337435.9	c.299C>A	p.Ala100Asp	missense_variant	3/5	1	NM_144599.5	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_noAF	Pathogenic	0.27
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.91	.;.;D
LIST_S2	Uncertain	0.93	.;D;D
MetaRNN	Pathogenic	0.90	D;D;D
PROVEAN	Pathogenic	-5.6	D;D;D
Sift	Pathogenic	0.0	D;D;D
Sift4G	Pathogenic	0.0	.;.;D
Vest4		0.96
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
gMVP		1.0

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-23060833;