chr16-79647-T-A

Position:

• chr16-79647-T-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001015052.3(MPG):​c.247T>A​(p.Leu83Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict 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: -1.19

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.053754658).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MPG	NM_001015052.3	c.247T>A	p.Leu83Met	missense_variant	2/4	ENST00000356432.8
MPG	NM_002434.4	c.262T>A	p.Leu88Met	missense_variant	3/5
MPG	NM_001015054.3	c.211T>A	p.Leu71Met	missense_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MPG	ENST00000356432.8	c.247T>A	p.Leu83Met	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

Dec 28, 2023

The c.262T>A (p.L88M) alteration is located in exon 3 (coding exon 2) of the MPG gene. This alteration results from a T to A substitution at nucleotide position 262, causing the leucine (L) at amino acid position 88 to be replaced by a methionine (M). 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	0.086
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	3.3
DANN	Benign	0.78
DEOGEN2	Benign	0.0093	T;.;.;T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.071	N
LIST_S2	Benign	0.80	T;T;T;T
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.054	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	.;.;.;N
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	0.27	N;N;N;N
REVEL	Benign	0.014
Sift	Benign	0.22	T;T;T;T
Sift4G	Benign	0.22	T;T;T;T
Polyphen		0.0050	B;.;.;B
Vest4		0.17, 0.17
MutPred		0.44		.;.;.;Gain of disorder (P = 0.2083);
MVP		0.25
MPC		0.054
ClinPred		0.083	T
GERP RS		-9.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.33
gMVP		0.27

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

LitVar

Other links and lift over

dbSNP: rs985687646; hg19: chr16-129646;