rs1158637890

Variant names:

• chr15-22786667-C-A
• rs1158637890
• NM_144599.5:c.11C>A

Your query was ambiguous. Multiple possible variants found:

• chr15-22786667-C-A
• chr15-22786667-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_144599.5(NIPA1):​c.11C>A​(p.Ala4Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000107 in 930,354 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 8/12 in silico tools predict a benign 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. A4V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000011 (0 hom.)
• Consequence: NIPA1 NM_144599.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.494
• 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: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16292372).

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.11C>A	p.Ala4Glu	missense	Exon 1 of 5	NP_653200.2
	NIPA1	NM_001142275.1		c.-48+419C>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.11C>A	p.Ala4Glu	missense	Exon 1 of 5	ENSP00000337452.4	Q7RTP0-1
	NIPA1	ENST00000437912.6	TSL:1	c.-48+12354C>A		intron	N/A	ENSP00000393962.2	Q7RTP0-2
	NIPA1	ENST00000561183.5	TSL:1	c.-48+419C>A		intron	N/A	ENSP00000453722.1	Q7RTP0-2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000107 AC: 1 AN: 930354 Hom.: 0 Cov.: 19 AF XY: 0.00000225 AC XY: 1 AN XY: 445264

African (AFR) AF: 0.00 AC: 0 AN: 17578

American (AMR) AF: 0.00 AC: 0 AN: 6806

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 8266

East Asian (EAS) AF: 0.00 AC: 0 AN: 8498

South Asian (SAS) AF: 0.00 AC: 0 AN: 22728

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7988

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2556

European-Non Finnish (NFE) AF: 0.00000121 AC: 1 AN: 823322

Other (OTH) AF: 0.00 AC: 0 AN: 32612

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_noAF	Benign	-0.28
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.041	T
LIST_S2	Benign	0.28	T
MetaRNN	Benign	0.16	T
PhyloP100		0.49
PROVEAN	Benign	0.63	N
Sift	Uncertain	0.025	D
Sift4G	Uncertain	0.059	T
Vest4		0.43
PromoterAI		0.12	Neutral
gMVP		0.75

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: rs1158637890; hg19: chr15-23086401;