15-22786362-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The ENST00000437912.6(NIPA1):c.-48+12049G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00881 in 153,700 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0089 (24 hom., cov: 32)
  • Exomes 𝑓: 0.00072 (0 hom.)
• Consequence: NIPA1 ENST00000437912.6 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.310

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 15-22786362-G-C is Benign according to our data. Variant chr15-22786362-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 1194677.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00888 (1353/152312) while in subpopulation AFR AF= 0.0307 (1278/41572). AF 95% confidence interval is 0.0293. There are 24 homozygotes in gnomad4. There are 641 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 1350 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NIPA1	NM_001142275.1	c.-48+114G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NIPA1	ENST00000437912.6	c.-48+12049G>C		intron_variant		1
NIPA1	ENST00000561183.5	c.-48+114G>C		intron_variant		1
NIPA1	ENST00000560069.5	n.31+114G>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.00887 AC: 1350 AN: 152194 Hom.: 24 Cov.: 32

Gnomad AFR AF: 0.0308

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00327

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00957

GnomAD4 exome AF: 0.000720 AC: 1 AN: 1388 Hom.: 0 AF XY: 0.00119 AC XY: 1 AN XY: 840

Gnomad4 AFR exome AF: 0.0385

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00888 AC: 1353 AN: 152312 Hom.: 24 Cov.: 32 AF XY: 0.00861 AC XY: 641 AN XY: 74482

Gnomad4 AFR AF: 0.0307

Gnomad4 AMR AF: 0.00327

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000735

Gnomad4 OTH AF: 0.00947

Alfa AF: 0.00763 Hom.: 2

Bravo AF: 0.0103

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 28, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	5.2
Dann	Benign	0.73

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs147356553; hg19: chr15-23086706;