15-22786701-G-C

Position:

• chr15-22786701-G-C

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_144599.5(NIPA1):​c.45G>C​(p.Ala15Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 29)
• Consequence: NIPA1 NM_144599.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00

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 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BP7: Synonymous conserved (PhyloP=0 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NIPA1	NM_144599.5	c.45G>C	p.Ala15Ala	synonymous_variant	1/5	ENST00000337435.9	NP_653200.2
NIPA1	NM_001142275.1	c.-48+453G>C		intron_variant			NP_001135747.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NIPA1	ENST00000337435.9	c.45G>C	p.Ala15Ala	synonymous_variant	1/5	1	NM_144599.5	ENSP00000337452.4
NIPA1	ENST00000437912.6	c.-48+12388G>C		intron_variant		1		ENSP00000393962.2
NIPA1	ENST00000561183.5	c.-48+453G>C		intron_variant		1		ENSP00000453722.1
NIPA1	ENST00000560069.5	n.31+453G>C		intron_variant		4

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	15
DANN	Benign	0.92
RBP_binding_hub_radar		1.0
RBP_regulation_power_radar		3.3

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: rs1555371616; hg19: chr15-23086367;