15-22786647-C-T

Variant names:

• chr15-22786647-C-T
• rs1285562776
• NM_144599.5:c.-10C>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.-10C>T variant causes a 5 prime UTR 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: 30)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NIPA1 NM_144599.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.513
• 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 (BayesDel_noAF=-0.34).

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.-10C>T		5_prime_UTR	Exon 1 of 5	NP_653200.2
	NIPA1	NM_001142275.1		c.-48+399C>T		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.-10C>T		5_prime_UTR	Exon 1 of 5	ENSP00000337452.4	Q7RTP0-1
	NIPA1	ENST00000437912.6	TSL:1	c.-48+12334C>T		intron	N/A	ENSP00000393962.2	Q7RTP0-2
	NIPA1	ENST00000561183.5	TSL:1	c.-48+399C>T		intron	N/A	ENSP00000453722.1	Q7RTP0-2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD2 exomes AF: 0.00 AC: 0 AN: 6644 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 859064 Hom.: 0 Cov.: 14 AF XY: 0.00 AC XY: 0 AN XY: 408032

African (AFR) AF: 0.00 AC: 0 AN: 16260

American (AMR) AF: 0.00 AC: 0 AN: 4056

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6744

East Asian (EAS) AF: 0.00 AC: 0 AN: 6242

South Asian (SAS) AF: 0.00 AC: 0 AN: 18940

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4914

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1888

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 770662

Other (OTH) AF: 0.00 AC: 0 AN: 29358

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	18
DANN	Uncertain	0.98
PhyloP100		-0.51
PromoterAI		-0.080	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		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

Other links and lift over

dbSNP: rs1285562776; hg19: chr15-23086421;