16-83118-CTG-GTA

Variant names:

• chr16-83118-CTG-GTA
• NM_001015052.3:c.367_369delCTGinsGTA
• MPG p.Leu123Val

Variant summary

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

The NM_001015052.3(MPG):​c.367_369delCTGinsGTA​(p.Leu123Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L123M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MPG NM_001015052.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.82
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

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.367_369delCTGinsGTA	p.Leu123Val	missense	N/A	NP_001015052.1	P29372-4
	MPG	NM_002434.4		c.382_384delCTGinsGTA	p.Leu128Val	missense	N/A	NP_002425.2	Q1W6H1
	MPG	NM_001015054.3		c.331_333delCTGinsGTA	p.Leu111Val	missense	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.367_369delCTGinsGTA	p.Leu123Val	missense	N/A	ENSP00000348809.4	P29372-4
	MPG	ENST00000219431.4	TSL:3	c.382_384delCTGinsGTA	p.Leu128Val	missense	N/A	ENSP00000219431.4	P29372-1
	MPG	ENST00000397817.5	TSL:2	c.331_333delCTGinsGTA	p.Leu111Val	missense	N/A	ENSP00000380918.1	P29372-5

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.8

Splicing

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

hg19: chr16-133117;