rs12899692

Variant names:

• chr15-22853459-C-T
• rs12899692
• NM_030922.7:c.196+191C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_030922.7(NIPA2):​c.196+191C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 150,960 control chromosomes in the GnomAD database, including 1,672 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.14 (1672 hom., cov: 27)
• Consequence: NIPA2 NM_030922.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.651
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BP6: Variant 15-22853459-C-T is Benign according to our data. Variant chr15-22853459-C-T is described in ClinVar as [Benign]. Clinvar id is 1281558.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.252 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NIPA2	NM_030922.7	c.196+191C>T		intron_variant	Intron 5 of 7	ENST00000337451.8	NP_112184.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NIPA2	ENST00000337451.8	c.196+191C>T		intron_variant	Intron 5 of 7	5	NM_030922.7	ENSP00000337618.3

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20434 AN: 150842 Hom.: 1665 Cov.: 27

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.258

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.0182

Gnomad SAS AF: 0.133

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.145

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

GnomAD4 genome AF: 0.136 AC: 20462 AN: 150960 Hom.: 1672 Cov.: 27 AF XY: 0.137 AC XY: 10132 AN XY: 73698

African (AFR) AF: 0.108 AC: 4430 AN: 41120

American (AMR) AF: 0.258 AC: 3907 AN: 15120

Ashkenazi Jewish (ASJ) AF: 0.141 AC: 490 AN: 3466

East Asian (EAS) AF: 0.0183 AC: 94 AN: 5140

South Asian (SAS) AF: 0.134 AC: 634 AN: 4746

European-Finnish (FIN) AF: 0.134 AC: 1385 AN: 10354

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.134 AC: 9078 AN: 67730

Other (OTH) AF: 0.143 AC: 298 AN: 2082

Alfa AF: 0.107 Hom.: 233

Bravo AF: 0.142

Asia WGS AF: 0.0810 AC: 279 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 15, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.076
DANN	Benign	0.38
PhyloP100		-0.65

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

Other links and lift over

dbSNP: rs12899692; hg19: chr15-23019609;