chr15-22853374-CTT-C

Variant names:

• chr15-22853373-TCT-TC
• rs35568106
• NM_030922.7:c.196+123delT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_030922.7(NIPA2):​c.196+123delT variant causes a intron change. The variant allele was found at a frequency of 0.154 in 377,258 control chromosomes in the GnomAD database, including 197 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.050 (171 hom., cov: 23)
  • Exomes 𝑓: 0.21 (26 hom.)
• Consequence: NIPA2 NM_030922.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.79
• Publications: 1 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: Benign. The variant received -10 ACMG points.

• BP6: Variant 15-22853373-TCT-TC is Benign according to our data. Variant chr15-22853374-CT-C is described in ClinVar as Benign. ClinVar VariationId is 1245041.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.207 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NIPA2	NM_030922.7	MANE Select	c.196+123delT		intron	N/A	NP_112184.4
	NIPA2	NM_001008860.3		c.196+123delT		intron	N/A	NP_001008860.1	Q8N8Q9-1
	NIPA2	NM_001008892.3		c.196+123delT		intron	N/A	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.196+107delT		intron	N/A	ENSP00000337618.3	Q8N8Q9-1
	NIPA2	ENST00000398013.7	TSL:1	c.196+107delT		intron	N/A	ENSP00000381095.3	Q8N8Q9-1
	NIPA2	ENST00000359727.8	TSL:1	c.139+1505delT		intron	N/A	ENSP00000352762.4	Q8N8Q9-2

Frequencies

GnomAD3 genomes AF: 0.0499 AC: 6848 AN: 137100 Hom.: 172 Cov.: 23

Gnomad AFR AF: 0.0478

Gnomad AMI AF: 0.00114

Gnomad AMR AF: 0.0440

Gnomad ASJ AF: 0.0832

Gnomad EAS AF: 0.217

Gnomad SAS AF: 0.0525

Gnomad FIN AF: 0.0257

Gnomad MID AF: 0.0925

Gnomad NFE AF: 0.0416

Gnomad OTH AF: 0.0489

GnomAD4 exome AF: 0.214 AC: 51391 AN: 240134 Hom.: 26 AF XY: 0.214 AC XY: 27784 AN XY: 129764

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

African (AFR) AF: 0.209 AC: 1251 AN: 5980

American (AMR) AF: 0.182 AC: 1670 AN: 9180

Ashkenazi Jewish (ASJ) AF: 0.217 AC: 1411 AN: 6490

East Asian (EAS) AF: 0.297 AC: 4536 AN: 15280

South Asian (SAS) AF: 0.216 AC: 4753 AN: 21954

European-Finnish (FIN) AF: 0.200 AC: 2841 AN: 14238

Middle Eastern (MID) AF: 0.199 AC: 234 AN: 1176

European-Non Finnish (NFE) AF: 0.209 AC: 32005 AN: 153308

Other (OTH) AF: 0.215 AC: 2690 AN: 12528

⚠️ 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.

GnomAD4 genome AF: 0.0500 AC: 6850 AN: 137124 Hom.: 171 Cov.: 23 AF XY: 0.0512 AC XY: 3374 AN XY: 65946

African (AFR) AF: 0.0479 AC: 1783 AN: 37186

American (AMR) AF: 0.0440 AC: 591 AN: 13440

Ashkenazi Jewish (ASJ) AF: 0.0832 AC: 273 AN: 3282

East Asian (EAS) AF: 0.218 AC: 1018 AN: 4676

South Asian (SAS) AF: 0.0520 AC: 226 AN: 4344

European-Finnish (FIN) AF: 0.0257 AC: 198 AN: 7708

Middle Eastern (MID) AF: 0.0858 AC: 23 AN: 268

European-Non Finnish (NFE) AF: 0.0416 AC: 2641 AN: 63472

Other (OTH) AF: 0.0512 AC: 96 AN: 1874

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	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.

Other links and lift over

dbSNP: rs35568106; hg19: chr15-23019695; COSMIC: COSV104399891; COSMIC: COSV104399891;