15-22786446-CG-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000437912.6(NIPA1):c.-48+12135del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0368 in 152,098 control chromosomes in the GnomAD database, including 351 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.037 (351 hom., cov: 31)
• Consequence: NIPA1 ENST00000437912.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.49

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 Benign. Variant got -10 ACMG points.

• BP6: Variant 15-22786446-CG-C is Benign according to our data. Variant chr15-22786446-CG-C is described in ClinVar as [Benign]. Clinvar id is 1298008.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.124 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NIPA1	NM_001142275.1	c.-48+200del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NIPA1	ENST00000437912.6	c.-48+12135del		intron_variant		1
NIPA1	ENST00000561183.5	c.-48+200del		intron_variant		1
NIPA1	ENST00000560069.5	n.31+200del		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.0366 AC: 5565 AN: 151984 Hom.: 349 Cov.: 31

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0121

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000620

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000883

Gnomad OTH AF: 0.0326

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

GnomAD4 genome AF: 0.0368 AC: 5590 AN: 152098 Hom.: 351 Cov.: 31 AF XY: 0.0352 AC XY: 2618 AN XY: 74380

Gnomad4 AFR AF: 0.127

Gnomad4 AMR AF: 0.0120

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000621

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000883

Gnomad4 OTH AF: 0.0323

Alfa AF: 0.0298 Hom.: 25

Bravo AF: 0.0406

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 20, 2019

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs142739374; hg19: chr15-23086622;