chr16-83128-A-G

Position:

• chr16-83128-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001015052.3(MPG):​c.377A>G​(p.Glu126Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MPG NM_001015052.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.79

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MPG	NM_001015052.3	c.377A>G	p.Glu126Gly	missense_variant	3/4	ENST00000356432.8
MPG	NM_002434.4	c.392A>G	p.Glu131Gly	missense_variant	4/5
MPG	NM_001015054.3	c.341A>G	p.Glu114Gly	missense_variant	3/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MPG	ENST00000356432.8	c.377A>G	p.Glu126Gly	missense_variant	3/4	1	NM_001015052.3	P2
MPG	ENST00000219431.4	c.392A>G	p.Glu131Gly	missense_variant	4/5	3		A2
MPG	ENST00000397817.5	c.341A>G	p.Glu114Gly	missense_variant	3/4	2		A2
MPG	ENST00000436333.5	c.341A>G	p.Glu114Gly	missense_variant	3/4	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 11, 2022

The c.392A>G (p.E131G) alteration is located in exon 4 (coding exon 3) of the MPG gene. This alteration results from a A to G substitution at nucleotide position 392, causing the glutamic acid (E) at amino acid position 131 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.071	T
BayesDel_noAF	Benign	-0.34
CADD	Pathogenic	28
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.026	T;.;.;T
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Pathogenic	0.99	D;D;D;D
M_CAP	Benign	0.035	D
MetaRNN	Uncertain	0.63	D;D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	.;.;.;L
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.59	T
PROVEAN	Pathogenic	-4.7	D;D;D;D
REVEL	Uncertain	0.30
Sift	Benign	0.030	D;T;D;T
Sift4G	Benign	0.10	T;T;T;T
Polyphen		0.99	D;.;.;D
Vest4		0.60, 0.60
MutPred		0.42		.;.;.;Loss of solvent accessibility (P = 0.0387);
MVP		0.65
MPC		0.33
ClinPred		1.0	D
GERP RS		4.9
Varity_R		0.63
gMVP		0.74

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-133127;