Genetic Variant NIPA2:c.196+120_196+123delTTTT (chr15-22853374-CTTTT-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_030922.7(NIPA2):c.196+120_196+123delTTTT variant causes a intron change. The variant allele was found at a frequency of 0.00306 in 378,628 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000073 ( 0 hom., cov: 23)

Exomes 𝑓: 0.0048 ( 0 hom. )

Consequence

NIPA2
NM_030922.7 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.79

Publications

1 publications found

Variant links:

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]

NIPA2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NIPA2	NM_030922.7	MANE Select	c.196+120_196+123delTTTT	intron	N/A	NP_112184.4
NIPA2	NM_001008860.3		c.196+120_196+123delTTTT	intron	N/A	NP_001008860.1	Q8N8Q9-1
NIPA2	NM_001008892.3		c.196+120_196+123delTTTT	intron	N/A	NP_001008892.1	Q8N8Q9-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NIPA2	ENST00000337451.8	TSL:5 MANE Select	c.196+107_196+110delTTTT	intron	N/A	ENSP00000337618.3	Q8N8Q9-1
NIPA2	ENST00000398013.7	TSL:1	c.196+107_196+110delTTTT	intron	N/A	ENSP00000381095.3	Q8N8Q9-1
NIPA2	ENST00000359727.8	TSL:1	c.139+1505_139+1508delTTTT	intron	N/A	ENSP00000352762.4	Q8N8Q9-2

Frequencies

GnomAD3 genomes

AF:

0.00000729

AC:

AN:

137226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000157

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00480

AC:

1159

AN:

241378

Hom.:

AF XY:

0.00475

AC XY:

620

AN XY:

130498

show subpopulations

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

African (AFR)

AF:

0.00517

AC:

AN:

5998

American (AMR)

AF:

0.00893

AC:

AN:

9178

Ashkenazi Jewish (ASJ)

AF:

0.00538

AC:

AN:

6506

East Asian (EAS)

AF:

0.00306

AC:

AN:

15376

South Asian (SAS)

AF:

0.00597

AC:

132

AN:

22094

European-Finnish (FIN)

AF:

0.00468

AC:

AN:

14328

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1180

European-Non Finnish (NFE)

AF:

0.00461

AC:

711

AN:

154126

Other (OTH)

AF:

0.00429

AC:

AN:

12592

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.262

Heterozygous variant carriers

121

242

362

483

604

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000729

AC:

AN:

137250

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

66000

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

37204

American (AMR)

AF:

0.00

AC:

AN:

13448

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3284

East Asian (EAS)

AF:

0.00

AC:

AN:

4686

South Asian (SAS)

AF:

0.00

AC:

AN:

4350

European-Finnish (FIN)

AF:

0.00

AC:

AN:

7712

Middle Eastern (MID)

AF:

0.00

AC:

AN:

268

European-Non Finnish (NFE)

AF:

0.0000157

AC:

AN:

63546

Other (OTH)

AF:

0.00

AC:

AN:

1878

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

3.8

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

Publications

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15-22853374-CTTTTTTT-CTTT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over