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15-22851830-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 2P and 17B. PP3_ModerateBP6_Very_StrongBP7BA1

The NM_030922.7(NIPA2):c.99G>A(p.Lys33=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 1,609,850 control chromosomes in the GnomAD database, including 29,321 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 3450 hom., cov: 31)
Exomes 𝑓: 0.18 ( 25871 hom. )

Consequence

NIPA2
NM_030922.7 synonymous

Scores

1
1

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.595
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

PP3
?
    PP3 - Multiple lines of computational evidence support a deleterious effect on the gene or gene product (conservation, evolutionary, splicing impact, etc.)
BayesDel_noAF computational evidence supports a deleterious effect, 0.31
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 15-22851830-G-A is Benign according to our data. Variant chr15-22851830-G-A is described in ClinVar as [Benign]. Clinvar id is 1221596.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.595 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.301 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NIPA2NM_030922.7 linkuse as main transcriptc.99G>A p.Lys33= synonymous_variant 4/8 ENST00000337451.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NIPA2ENST00000337451.8 linkuse as main transcriptc.99G>A p.Lys33= synonymous_variant 4/85 NM_030922.7 P1Q8N8Q9-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.206
AC:
31192
AN:
151644
Hom.:
3442
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.229
Gnomad AMI
AF:
0.111
Gnomad AMR
AF:
0.307
Gnomad ASJ
AF:
0.225
Gnomad EAS
AF:
0.251
Gnomad SAS
AF:
0.195
Gnomad FIN
AF:
0.157
Gnomad MID
AF:
0.253
Gnomad NFE
AF:
0.173
Gnomad OTH
AF:
0.216
GnomAD3 exomes
AF:
0.215
AC:
53577
AN:
249672
Hom.:
6574
AF XY:
0.208
AC XY:
28027
AN XY:
135024
show subpopulations
Gnomad AFR exome
AF:
0.234
Gnomad AMR exome
AF:
0.382
Gnomad ASJ exome
AF:
0.215
Gnomad EAS exome
AF:
0.237
Gnomad SAS exome
AF:
0.200
Gnomad FIN exome
AF:
0.160
Gnomad NFE exome
AF:
0.173
Gnomad OTH exome
AF:
0.201
GnomAD4 exome
AF:
0.181
AC:
264482
AN:
1458086
Hom.:
25871
Cov.:
32
AF XY:
0.181
AC XY:
131596
AN XY:
725452
show subpopulations
Gnomad4 AFR exome
AF:
0.233
Gnomad4 AMR exome
AF:
0.372
Gnomad4 ASJ exome
AF:
0.221
Gnomad4 EAS exome
AF:
0.218
Gnomad4 SAS exome
AF:
0.199
Gnomad4 FIN exome
AF:
0.162
Gnomad4 NFE exome
AF:
0.169
Gnomad4 OTH exome
AF:
0.192
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.206
AC:
31230
AN:
151764
Hom.:
3450
Cov.:
31
AF XY:
0.207
AC XY:
15388
AN XY:
74170
show subpopulations
Gnomad4 AFR
AF:
0.229
Gnomad4 AMR
AF:
0.308
Gnomad4 ASJ
AF:
0.225
Gnomad4 EAS
AF:
0.252
Gnomad4 SAS
AF:
0.195
Gnomad4 FIN
AF:
0.157
Gnomad4 NFE
AF:
0.173
Gnomad4 OTH
AF:
0.215
Alfa
AF:
0.175
Hom.:
3710
Bravo
AF:
0.217
Asia WGS
AF:
0.223
AC:
776
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxMay 04, 2021- -
NIPA2-related disorder Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesOct 23, 2019This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Pathogenic
0.31
Cadd
Benign
6.7
Dann
Benign
0.71
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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

Publications

LitVar

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

Other links and lift over

dbSNP: rs7170838; hg19: chr15-23021238; COSMIC: COSV61682373; COSMIC: COSV61682373; API