chr15-22860655-A-T

Variant names:

• chr15-22860655-A-T
• rs748494134
• NM_030922.7:c.314A>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_030922.7(NIPA2):​c.314A>T​(p.Asn105Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000698 in 1,432,100 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N105S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: NIPA2 NM_030922.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.14
• 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: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.824

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NIPA2	NM_030922.7	c.314A>T	p.Asn105Ile	missense_variant	Exon 7 of 8	ENST00000337451.8	NP_112184.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NIPA2	ENST00000337451.8	c.314A>T	p.Asn105Ile	missense_variant	Exon 7 of 8	5	NM_030922.7	ENSP00000337618.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.98e-7 AC: 1 AN: 1432100 Hom.: 0 Cov.: 28 AF XY: 0.00000141 AC XY: 1 AN XY: 711640

African (AFR) AF: 0.00 AC: 0 AN: 31928

American (AMR) AF: 0.00 AC: 0 AN: 36710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25366

East Asian (EAS) AF: 0.00 AC: 0 AN: 38322

South Asian (SAS) AF: 0.00 AC: 0 AN: 79068

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53178

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5694

European-Non Finnish (NFE) AF: 9.07e-7 AC: 1 AN: 1102612

Other (OTH) AF: 0.00 AC: 0 AN: 59222

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.62
BayesDel_noAF	Benign	-0.31
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Pathogenic	0.89	D;.;D;D;.
LIST_S2	Uncertain	0.95	D;D;.;.;.
MetaRNN	Pathogenic	0.82	D;D;D;D;D
PhyloP100		3.1
PROVEAN	Pathogenic	-5.5	D;D;D;D;D
Sift	Benign	0.031	D;D;D;D;D
Sift4G	Benign	0.073	T;T;T;T;T
Vest4		0.81
gMVP		0.89

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs748494134; hg19: chr15-23012413;