Variant 16-83097-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001015052.3(MPG):c.346A>G(p.Ile116Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000548 in 1,459,958 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

MPG
NM_001015052.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.970

Variant links:

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 links:

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ACMG classification

Classification made for transcript

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=0.3431526).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
MPG	NM_001015052.3 linkuse as main transcript	c.346A>G	p.Ile116Val	missense_variant	3/4	ENST00000356432.8
MPG	NM_002434.4 linkuse as main transcript	c.361A>G	p.Ile121Val	missense_variant	4/5
MPG	NM_001015054.3 linkuse as main transcript	c.310A>G	p.Ile104Val	missense_variant	3/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MPG	ENST00000356432.8 linkuse as main transcript	c.346A>G	p.Ile116Val	missense_variant	3/4	1	NM_001015052.3	P2	P29372-4
MPG	ENST00000219431.4 linkuse as main transcript	c.361A>G	p.Ile121Val	missense_variant	4/5	3		A2	P29372-1
MPG	ENST00000397817.5 linkuse as main transcript	c.310A>G	p.Ile104Val	missense_variant	3/4	2		A2	P29372-5
MPG	ENST00000436333.5 linkuse as main transcript	c.310A>G	p.Ile104Val	missense_variant	3/4	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000400

AC:

AN:

249792

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135118

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000888

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000548

AC:

AN:

1459958

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726134

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000630

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 31, 2023

The c.361A>G (p.I121V) 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 361, causing the isoleucine (I) at amino acid position 121 to be replaced by a valine (V). 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

0.095

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.47

CADD

Benign

5.8

DANN

Uncertain

0.98

DEOGEN2

Benign

0.057

T;.;.;T

Eigen

Benign

-0.30

Eigen_PC

Benign

-0.31

FATHMM_MKL

Benign

0.65

LIST_S2

Benign

0.84

T;T;D;T

M_CAP

Benign

0.0078

MetaRNN

Benign

0.34

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.6

.;.;.;M

MutationTaster

Benign

0.98

D;D;D

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.84

N;N;N;N

REVEL

Benign

0.10

Sift

Benign

0.064

T;T;T;D

Sift4G

Benign

0.082

T;T;T;T

Polyphen

0.41

B;.;.;B

Vest4

0.18, 0.19, 0.19

MutPred

0.72

.;.;.;Gain of methylation at R120 (P = 0.045);

MVP

0.18

MPC

0.057

ClinPred

0.19

GERP RS

1.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.20

gMVP

0.62

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over