rs2562182

Variant names:

• chr16-83947-G-A
• rs2562182
• NM_001015052.3:c.505+691G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001015052.3(MPG):​c.505+691G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.714 in 151,924 control chromosomes in the GnomAD database, including 41,739 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.71 (41739 hom., cov: 30)
• Consequence: MPG NM_001015052.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.73
• Publications: 13 publications found

Genes affected

MPG (HGNC:7211): (N-methylpurine DNA glycosylase) Predicted to enable alkylbase DNA N-glycosylase activity. Predicted to be involved in base-excision repair. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

NPRL3 (HGNC:14124): (NPR3 like, GATOR1 complex subunit) Contributes to GTPase activator activity. Involved in cellular response to amino acid starvation and negative regulation of TOR signaling. Located in lysosomal membrane. Part of GATOR1 complex. Implicated in focal epilepsy. [provided by Alliance of Genome Resources, Apr 2022]

NPRL3 Gene-Disease associations (from GenCC):

• focal epilepsy

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• epilepsy, familial focal, with variable foci 3

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• familial focal epilepsy with variable foci

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.839 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001015052.3. 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
	MPG	NM_001015052.3	MANE Select	c.505+691G>A		intron	N/A	NP_001015052.1	P29372-4
	MPG	NM_002434.4		c.520+691G>A		intron	N/A	NP_002425.2	Q1W6H1
	MPG	NM_001015054.3		c.469+691G>A		intron	N/A	NP_001015054.1	P29372-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPG	ENST00000356432.8	TSL:1 MANE Select	c.505+691G>A		intron	N/A	ENSP00000348809.4	P29372-4
	NPRL3	ENST00000882131.1		c.*686C>T		3_prime_UTR	Exon 14 of 14	ENSP00000552190.1
	NPRL3	ENST00000882130.1		c.*686C>T		3_prime_UTR	Exon 13 of 13	ENSP00000552189.1

Frequencies

GnomAD3 genomes AF: 0.714 AC: 108365 AN: 151806 Hom.: 41717 Cov.: 30

Gnomad AFR AF: 0.400

Gnomad AMI AF: 0.776

Gnomad AMR AF: 0.820

Gnomad ASJ AF: 0.860

Gnomad EAS AF: 0.704

Gnomad SAS AF: 0.856

Gnomad FIN AF: 0.820

Gnomad MID AF: 0.775

Gnomad NFE AF: 0.845

Gnomad OTH AF: 0.754

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.714 AC: 108407 AN: 151924 Hom.: 41739 Cov.: 30 AF XY: 0.717 AC XY: 53228 AN XY: 74266

African (AFR) AF: 0.400 AC: 16546 AN: 41374

American (AMR) AF: 0.821 AC: 12520 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.860 AC: 2984 AN: 3470

East Asian (EAS) AF: 0.704 AC: 3621 AN: 5142

South Asian (SAS) AF: 0.857 AC: 4129 AN: 4818

European-Finnish (FIN) AF: 0.820 AC: 8666 AN: 10574

Middle Eastern (MID) AF: 0.779 AC: 229 AN: 294

European-Non Finnish (NFE) AF: 0.845 AC: 57411 AN: 67980

Other (OTH) AF: 0.757 AC: 1598 AN: 2110

Alfa AF: 0.815 Hom.: 89425

Bravo AF: 0.696

Asia WGS AF: 0.775 AC: 2696 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.2
DANN	Benign	0.41
PhyloP100		1.7
Mutation Taster		=100/0	polymorphism (auto)

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: rs2562182;

hg19: chr16-133946;

COSMIC: COSV54739645;

COSMIC: COSV54739645;