chr15-22860655-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_030922.7(NIPA2):ā€‹c.314A>Gā€‹(p.Asn105Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000884 in 1,584,260 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 8/12 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 33)
Exomes š‘“: 0.0000091 ( 0 hom. )

Consequence

NIPA2
NM_030922.7 missense

Scores

2
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.14
Variant links:
Genes affected
NIPA2 (HGNC:17044): (NIPA magnesium transporter 2) This gene encodes a possible magnesium transporter. This gene is located adjacent to the imprinted domain in the Prader-Willi syndrome deletion region of chromosome 15. Alternate splicing results in multiple transcript variants. Pseudogenes of this gene are found on chromosomes 3, 7 and 21.[provided by RefSeq, May 2010]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.21586591).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
NIPA2NM_030922.7 linkuse as main transcriptc.314A>G p.Asn105Ser missense_variant 7/8 ENST00000337451.8 NP_112184.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
NIPA2ENST00000337451.8 linkuse as main transcriptc.314A>G p.Asn105Ser missense_variant 7/85 NM_030922.7 ENSP00000337618 P1Q8N8Q9-1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152160
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000181
AC:
4
AN:
220458
Hom.:
0
AF XY:
0.0000251
AC XY:
3
AN XY:
119454
show subpopulations
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 SAS exome
AF:
0.0000866
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000387
GnomAD4 exome
AF:
0.00000908
AC:
13
AN:
1432100
Hom.:
0
Cov.:
28
AF XY:
0.00000984
AC XY:
7
AN XY:
711640
show subpopulations
Gnomad4 AFR exome
AF:
0.0000626
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000632
Gnomad4 FIN exome
AF:
0.0000564
Gnomad4 NFE exome
AF:
0.00000181
Gnomad4 OTH exome
AF:
0.0000169
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152160
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74326
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJul 05, 2023The c.314A>G (p.N105S) alteration is located in exon 9 (coding exon 4) of the NIPA2 gene. This alteration results from a A to G substitution at nucleotide position 314, causing the asparagine (N) at amino acid position 105 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.081
BayesDel_noAF
Benign
-0.40
CADD
Benign
17
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.75
D;.;D;D;.
LIST_S2
Benign
0.80
T;T;.;.;.
MetaRNN
Benign
0.22
T;T;T;T;T
PROVEAN
Benign
-2.1
N;N;N;N;N
Sift
Benign
0.084
T;T;T;T;T
Sift4G
Benign
0.19
T;T;T;T;T
Vest4
0.22
gMVP
0.34

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

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.

Other links and lift over

dbSNP: rs748494134; hg19: chr15-23012413; API