NM_030922.7:c.-58C>A

Variant names:

• chr15-22851674-C-A
• rs117894530
• NM_030922.7:c.-58C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_030922.7(NIPA2):​c.-58C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000767 in 1,303,872 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.7e-7 (0 hom.)
• Consequence: NIPA2 NM_030922.7 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.568
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NIPA2	NM_030922.7	c.-58C>A		5_prime_UTR_variant	Exon 4 of 8	ENST00000337451.8	NP_112184.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NIPA2	ENST00000337451.8	c.-58C>A		5_prime_UTR_variant	Exon 4 of 8	5	NM_030922.7	ENSP00000337618.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.67e-7 AC: 1 AN: 1303872 Hom.: 0 Cov.: 17 AF XY: 0.00000154 AC XY: 1 AN XY: 650846

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 28720

American (AMR) AF: 0.00 AC: 0 AN: 30778

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22682

East Asian (EAS) AF: 0.00 AC: 0 AN: 38272

South Asian (SAS) AF: 0.00 AC: 0 AN: 72106

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51220

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5242

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1000626

Other (OTH) AF: 0.0000184 AC: 1 AN: 54226

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	13
DANN	Benign	0.79
PhyloP100		0.57
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.17		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: rs117894530; hg19: chr15-23021394;