15-22851674-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_030922.7(NIPA2):c.-58C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0241 in 1,455,732 control chromosomes in the GnomAD database, including 590 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.019 (45 hom., cov: 32)
  • Exomes 𝑓: 0.025 (545 hom.)
• Consequence: NIPA2 NM_030922.7 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.568

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

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 15-22851674-C-T is Benign according to our data. Variant chr15-22851674-C-T is described in ClinVar as [Benign]. Clinvar id is 1248113.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0193 (2935/152188) while in subpopulation NFE AF= 0.0247 (1680/68000). AF 95% confidence interval is 0.0237. There are 45 homozygotes in gnomad4. There are 1518 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 45 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NIPA2	NM_030922.7	c.-58C>T		5_prime_UTR_variant	4/8	ENST00000337451.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NIPA2	ENST00000337451.8	c.-58C>T		5_prime_UTR_variant	4/8	5	NM_030922.7	P1

Frequencies

GnomAD3 genomes AF: 0.0193 AC: 2935 AN: 152070 Hom.: 45 Cov.: 32

Gnomad AFR AF: 0.00432

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0109

Gnomad ASJ AF: 0.0196

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00850

Gnomad FIN AF: 0.0734

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.0247

Gnomad OTH AF: 0.0110

GnomAD4 exome AF: 0.0247 AC: 32134 AN: 1303544 Hom.: 545 Cov.: 17 AF XY: 0.0243 AC XY: 15803 AN XY: 650708

Gnomad4 AFR exome AF: 0.00303

Gnomad4 AMR exome AF: 0.00760

Gnomad4 ASJ exome AF: 0.0190

Gnomad4 EAS exome AF: 0.0000784

Gnomad4 SAS exome AF: 0.00893

Gnomad4 FIN exome AF: 0.0780

Gnomad4 NFE exome AF: 0.0255

Gnomad4 OTH exome AF: 0.0220

GnomAD4 genome AF: 0.0193 AC: 2935 AN: 152188 Hom.: 45 Cov.: 32 AF XY: 0.0204 AC XY: 1518 AN XY: 74384

Gnomad4 AFR AF: 0.00431

Gnomad4 AMR AF: 0.0109

Gnomad4 ASJ AF: 0.0196

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00871

Gnomad4 FIN AF: 0.0734

Gnomad4 NFE AF: 0.0247

Gnomad4 OTH AF: 0.0104

Alfa AF: 0.0203 Hom.: 8

Bravo AF: 0.0145

Asia WGS AF: 0.00520 AC: 18 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 13, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	18
Dann	Benign	0.83
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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

Other links and lift over

dbSNP: rs117894530; hg19: chr15-23021394;