NM_030922.7:c.233C>T

Variant names:

• chr15-22858576-C-T
• rs140858794
• NM_030922.7:c.233C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_030922.7(NIPA2):​c.233C>T​(p.Ala78Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000225 in 1,605,862 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. A78A) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00019 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00023 (2 hom.)
• Consequence: NIPA2 NM_030922.7 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 7.76
• Publications: 3 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 -4 ACMG points.

• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030922.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NIPA2	NM_030922.7	MANE Select	c.233C>T	p.Ala78Val	missense	Exon 6 of 8	NP_112184.4
	NIPA2	NM_001008860.3		c.233C>T	p.Ala78Val	missense	Exon 5 of 7	NP_001008860.1	Q8N8Q9-1
	NIPA2	NM_001008892.3		c.233C>T	p.Ala78Val	missense	Exon 4 of 6	NP_001008892.1	Q8N8Q9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NIPA2	ENST00000337451.8	TSL:5 MANE Select	c.233C>T	p.Ala78Val	missense	Exon 6 of 8	ENSP00000337618.3	Q8N8Q9-1
	NIPA2	ENST00000398013.7	TSL:1	c.233C>T	p.Ala78Val	missense	Exon 4 of 6	ENSP00000381095.3	Q8N8Q9-1
	NIPA2	ENST00000359727.8	TSL:1	c.176C>T	p.Ala59Val	missense	Exon 4 of 6	ENSP00000352762.4	Q8N8Q9-2

Frequencies

GnomAD3 genomes AF: 0.000191 AC: 29 AN: 152094 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000724

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: 0.000661

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000279

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000275 AC: 66 AN: 240408 AF XY: 0.000262

Gnomad AFR exome AF: 0.0000658

Gnomad AMR exome AF: 0.0000894

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000571

Gnomad NFE exome AF: 0.000437

Gnomad OTH exome AF: 0.000169

GnomAD4 exome AF: 0.000229 AC: 333 AN: 1453768 Hom.: 2 Cov.: 29 AF XY: 0.000212 AC XY: 153 AN XY: 722388

African (AFR) AF: 0.0000599 AC: 2 AN: 33366

American (AMR) AF: 0.0000909 AC: 4 AN: 44014

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25918

East Asian (EAS) AF: 0.00 AC: 0 AN: 39482

South Asian (SAS) AF: 0.0000353 AC: 3 AN: 85084

European-Finnish (FIN) AF: 0.000908 AC: 48 AN: 52872

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5746

European-Non Finnish (NFE) AF: 0.000240 AC: 266 AN: 1107280

Other (OTH) AF: 0.000167 AC: 10 AN: 60006

GnomAD4 genome AF: 0.000191 AC: 29 AN: 152094 Hom.: 0 Cov.: 33 AF XY: 0.000175 AC XY: 13 AN XY: 74282

African (AFR) AF: 0.0000724 AC: 3 AN: 41420

American (AMR) AF: 0.00 AC: 0 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.000661 AC: 7 AN: 10590

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000279 AC: 19 AN: 68014

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.000288 Hom.: 0

Bravo AF: 0.000125

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.41
BayesDel_noAF	Pathogenic	0.38
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.82	D
LIST_S2	Uncertain	0.93	D
MetaRNN	Uncertain	0.66	D
PhyloP100		7.8
PROVEAN	Uncertain	-2.7	D
Sift	Benign	0.030	D
Sift4G	Benign	0.061	T
Vest4		0.82
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.94
Mutation Taster		=23/77	disease causing

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: rs140858794; hg19: chr15-23014492; COSMIC: COSV99047059;