16-79602-A-G

Position:

• chr16-79602-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001015052.3(MPG):​c.202A>G​(p.Ser68Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: MPG NM_001015052.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.88

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38773715).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MPG	NM_001015052.3	c.202A>G	p.Ser68Gly	missense_variant	2/4	ENST00000356432.8
MPG	NM_002434.4	c.217A>G	p.Ser73Gly	missense_variant	3/5
MPG	NM_001015054.3	c.166A>G	p.Ser56Gly	missense_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MPG	ENST00000356432.8	c.202A>G	p.Ser68Gly	missense_variant	2/4	1	NM_001015052.3	P2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

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

Jan 29, 2024

The c.217A>G (p.S73G) alteration is located in exon 3 (coding exon 2) of the MPG gene. This alteration results from a A to G substitution at nucleotide position 217, causing the serine (S) at amino acid position 73 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	0.21
BayesDel_addAF	Uncertain	0.028	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.033	T;.;.;T
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.77	T;T;T;T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.39	T;T;T;T
MetaSVM	Benign	-1.2	T
MutationAssessor	Benign	1.6	.;.;.;L
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-1.8	N;N;N;N
REVEL	Benign	0.19
Sift	Uncertain	0.012	D;D;D;D
Sift4G	Pathogenic	0.0	D;D;D;D
Polyphen		1.0	D;.;.;D
Vest4		0.58, 0.57, 0.68
MutPred		0.17		.;.;.;Loss of phosphorylation at S73 (P = 0.0269);
MVP		0.64
MPC		0.34
ClinPred		0.92	D
GERP RS		5.1
Varity_R		0.29
gMVP		0.49

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: chr16-129601;