Genetic Variant NIPA2:c.196+122_196+123delTT (chr15-22853374-CTT-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_030922.7(NIPA2):c.196+122_196+123delTT variant causes a intron change. The variant allele was found at a frequency of 0.152 in 373,554 control chromosomes in the GnomAD database, including 1,478 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.15 ( 1250 hom., cov: 23)

Exomes 𝑓: 0.15 ( 228 hom. )

Consequence

NIPA2
NM_030922.7 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 15-22853374-CTT-C is Benign according to our data. Variant chr15-22853374-CTT-C is described in ClinVar as Benign. ClinVar VariationId is 1260282.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.243 is higher than 0.05.

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+122_196+123delTT	intron	N/A	NP_112184.4
NIPA2	NM_001008860.3		c.196+122_196+123delTT	intron	N/A	NP_001008860.1	Q8N8Q9-1
NIPA2	NM_001008892.3		c.196+122_196+123delTT	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+108delTT	intron	N/A	ENSP00000337618.3	Q8N8Q9-1
NIPA2	ENST00000398013.7	TSL:1	c.196+107_196+108delTT	intron	N/A	ENSP00000381095.3	Q8N8Q9-1
NIPA2	ENST00000359727.8	TSL:1	c.139+1505_139+1506delTT	intron	N/A	ENSP00000352762.4	Q8N8Q9-2

Frequencies

GnomAD3 genomes

AF:

0.153

AC:

20913

AN:

136808

Hom.:

1242

Cov.:

show subpopulations

Gnomad AFR

AF:

0.183

Gnomad AMI

AF:

0.106

Gnomad AMR

AF:

0.249

Gnomad ASJ

AF:

0.140

Gnomad EAS

AF:

0.0183

Gnomad SAS

AF:

0.136

Gnomad FIN

AF:

0.117

Gnomad MID

AF:

0.145

Gnomad NFE

AF:

0.132

Gnomad OTH

AF:

0.162

GnomAD4 exome

AF:

0.151

AC:

35818

AN:

236718

Hom.:

228

AF XY:

0.151

AC XY:

19346

AN XY:

127868

show subpopulations

African (AFR)

AF:

0.187

AC:

1107

AN:

5924

American (AMR)

AF:

0.251

AC:

2287

AN:

9126

Ashkenazi Jewish (ASJ)

AF:

0.160

AC:

1022

AN:

6402

East Asian (EAS)

AF:

0.0795

AC:

1195

AN:

15034

South Asian (SAS)

AF:

0.169

AC:

3654

AN:

21610

European-Finnish (FIN)

AF:

0.149

AC:

2086

AN:

14010

Middle Eastern (MID)

AF:

0.166

AC:

194

AN:

1168

European-Non Finnish (NFE)

AF:

0.148

AC:

22382

AN:

151120

Other (OTH)

AF:

0.153

AC:

1891

AN:

12324

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.411

Heterozygous variant carriers

1510

3020

4529

6039

7549

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

262

524

786

1048

1310

<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:

0.153

AC:

20939

AN:

136836

Hom.:

1250

Cov.:

AF XY:

0.152

AC XY:

9982

AN XY:

65774

show subpopulations

African (AFR)

AF:

0.183

AC:

6781

AN:

37094

American (AMR)

AF:

0.250

AC:

3342

AN:

13390

Ashkenazi Jewish (ASJ)

AF:

0.140

AC:

459

AN:

3282

East Asian (EAS)

AF:

0.0184

AC:

AN:

4686

South Asian (SAS)

AF:

0.136

AC:

590

AN:

4336

European-Finnish (FIN)

AF:

0.117

AC:

897

AN:

7676

Middle Eastern (MID)

AF:

0.154

AC:

AN:

266

European-Non Finnish (NFE)

AF:

0.132

AC:

8349

AN:

63352

Other (OTH)

AF:

0.160

AC:

301

AN:

1880

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

685

1370

2054

2739

3424

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

234

468

702

936

1170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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chr15-22853375-TTTTTT-TTTT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over