15-22794684-T-C

Variant names:

• chr15-22794684-T-C
• rs7174119
• NM_144599.5:c.178+7850T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_144599.5(NIPA1):​c.178+7850T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.694 in 151,798 control chromosomes in the GnomAD database, including 37,236 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 0.69 (37236 hom., cov: 30)
• Consequence: NIPA1 NM_144599.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.317
• Publications: 5 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: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.889 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NIPA1	NM_144599.5	c.178+7850T>C		intron_variant	Intron 1 of 4	ENST00000337435.9	NP_653200.2
NIPA1	NM_001142275.1	c.-48+8436T>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.178+7850T>C		intron_variant	Intron 1 of 4	1	NM_144599.5	ENSP00000337452.4

Frequencies

GnomAD3 genomes AF: 0.694 AC: 105294 AN: 151678 Hom.: 37190 Cov.: 30

Gnomad AFR AF: 0.790

Gnomad AMI AF: 0.814

Gnomad AMR AF: 0.728

Gnomad ASJ AF: 0.630

Gnomad EAS AF: 0.911

Gnomad SAS AF: 0.793

Gnomad FIN AF: 0.597

Gnomad MID AF: 0.684

Gnomad NFE AF: 0.622

Gnomad OTH AF: 0.676

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.694 AC: 105402 AN: 151798 Hom.: 37236 Cov.: 30 AF XY: 0.697 AC XY: 51662 AN XY: 74152

African (AFR) AF: 0.791 AC: 32729 AN: 41400

American (AMR) AF: 0.729 AC: 11124 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.630 AC: 2186 AN: 3470

East Asian (EAS) AF: 0.910 AC: 4688 AN: 5150

South Asian (SAS) AF: 0.793 AC: 3816 AN: 4810

European-Finnish (FIN) AF: 0.597 AC: 6271 AN: 10512

Middle Eastern (MID) AF: 0.687 AC: 202 AN: 294

European-Non Finnish (NFE) AF: 0.622 AC: 42230 AN: 67886

Other (OTH) AF: 0.675 AC: 1414 AN: 2096

Alfa AF: 0.650 Hom.: 126029

Bravo AF: 0.709

Asia WGS AF: 0.820 AC: 2851 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.7
DANN	Benign	0.64
PhyloP100		-0.32

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: rs7174119; hg19: chr15-23078384;