Variant 15-22786362-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001142275.1(NIPA1):c.-48+114G>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
NM_001142275.1 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.310

Variant links:

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 links:

NIPA1 (HGNC:):

NIPA1 links:

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ACMG classification

Classification made for transcript

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 GnomAd4 at 1353 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NIPA1	NM_001142275.1 linkuse as main transcript	c.-48+114G>C		intron_variant			NP_001135747.1	Q7RTP0-2A0A024R344Q8TAY1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	Protein	UniProt
NIPA1	ENST00000437912.6 linkuse as main transcript	c.-48+12049G>C	intron_variant	1	ENSP00000393962.2	Q7RTP0-2
NIPA1	ENST00000561183.5 linkuse as main transcript	c.-48+114G>C	intron_variant	1	ENSP00000453722.1	Q7RTP0-2
NIPA1	ENST00000560069.5 linkuse as main transcript	n.31+114G>C	intron_variant	4

Frequencies

GnomAD3 genomes

AF:

0.00887

AC:

1350

AN:

152194

Hom.:

Cov.:

show subpopulations

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:

AN:

1388

Hom.:

AF XY:

0.00119

AC XY:

AN XY:

840

show subpopulations

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.:

Cov.:

AF XY:

0.00861

AC XY:

641

AN XY:

74482

show subpopulations

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.:

Bravo

AF:

0.0103

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 28, 2019

- -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over