NM_144599.5:c.1A>C

Variant names:

• chr15-22786657-A-C
• rs1310579113
• NM_144599.5:c.1A>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PVS1_Moderate BS2

The NM_144599.5(NIPA1):​c.1A>C​(p.Met1?) variant causes a initiator codon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000423 in 1,017,508 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000048 (0 hom., cov: 30)
  • Exomes 𝑓: 0.000041 (0 hom.)
• Consequence: NIPA1 NM_144599.5 initiator_codon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.19

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 Likely_benign. Variant got -2 ACMG points.

• PVS1: Start lost variant, next in-frame start position is after 1 pathogenic variants. Next in-frame start position is after 76 codons. Genomic position: 22810796. Lost 0.228 part of the original CDS.
• BS2: High AC in GnomAd4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NIPA1	NM_144599.5	c.1A>C	p.Met1?	initiator_codon_variant	Exon 1 of 5	ENST00000337435.9	NP_653200.2
NIPA1	NM_001142275.1	c.-48+409A>C		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.1A>C	p.Met1?	initiator_codon_variant	Exon 1 of 5	1	NM_144599.5	ENSP00000337452.4

Frequencies

GnomAD3 genomes AF: 0.0000482 AC: 7 AN: 145292 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.0000250

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000680

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000421

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000456

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000413 AC: 36 AN: 872122 Hom.: 0 Cov.: 17 AF XY: 0.0000503 AC XY: 21 AN XY: 417406

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000472

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000438

Gnomad4 OTH exome AF: 0.0000331

GnomAD4 genome AF: 0.0000481 AC: 7 AN: 145386 Hom.: 0 Cov.: 30 AF XY: 0.0000282 AC XY: 2 AN XY: 70858

Gnomad4 AFR AF: 0.0000249

Gnomad4 AMR AF: 0.0000679

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000422

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000456

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	18
DANN	Benign	0.89
DEOGEN2	Benign	0.041	T
LIST_S2	Uncertain	0.90	D
MetaRNN	Benign	0.38	T
PROVEAN	Benign	0.070	N
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Vest4		0.44
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.42

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1310579113; hg19: chr15-23086411;