16-79493-C-G

Variant names:

• chr16-79493-C-G
• rs2266605
• NM_001015052.3:c.93C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001015052.3(MPG):​c.93C>G​(p.Asp31Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,460,574 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. D31D) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: MPG NM_001015052.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.171
• Publications: 5 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]

MPG Gene-Disease associations (from GenCC):

• schizophrenia

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05012375).

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.93C>G	p.Asp31Glu	missense	Exon 2 of 4	NP_001015052.1	P29372-4
	MPG	NM_002434.4		c.108C>G	p.Asp36Glu	missense	Exon 3 of 5	NP_002425.2	Q1W6H1
	MPG	NM_001015054.3		c.57C>G	p.Asp19Glu	missense	Exon 2 of 4	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.93C>G	p.Asp31Glu	missense	Exon 2 of 4	ENSP00000348809.4	P29372-4
	MPG	ENST00000219431.4	TSL:3	c.108C>G	p.Asp36Glu	missense	Exon 3 of 5	ENSP00000219431.4	P29372-1
	MPG	ENST00000397817.5	TSL:2	c.57C>G	p.Asp19Glu	missense	Exon 2 of 4	ENSP00000380918.1	P29372-5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1460574 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 726610

African (AFR) AF: 0.0000299 AC: 1 AN: 33470

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52364

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111806

Other (OTH) AF: 0.00 AC: 0 AN: 60362

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 2

Bravo AF: 0.0000151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.59
DANN	Benign	0.36
DEOGEN2	Benign	0.0051	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.035	N
LIST_S2	Benign	0.29	T
M_CAP	Benign	0.0012	T
MetaRNN	Benign	0.050	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.17
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-0.040	N
REVEL	Benign	0.013
Sift	Benign	0.24	T
Sift4G	Benign	1.0	T
Polyphen		0.037	B
Vest4		0.074
MutPred		0.13		Gain of helix (P = 0.062)
MVP		0.30
MPC		0.054
ClinPred		0.041	T
GERP RS		-0.34
Varity_R		0.025
gMVP		0.17
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs2266605; hg19: chr16-129492;