16-83118-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001015052.3(MPG):​c.367C>G​(p.Leu123Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000049 in 1,612,970 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L123M) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000053 ( 0 hom. )

Consequence

MPG
NM_001015052.3 missense

Scores

5
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.496
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.23891544).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MPGNM_001015052.3 linkc.367C>G p.Leu123Val missense_variant Exon 3 of 4 ENST00000356432.8 NP_001015052.1 P29372-4
MPGNM_002434.4 linkc.382C>G p.Leu128Val missense_variant Exon 4 of 5 NP_002425.2 P29372-1Q1W6H1
MPGNM_001015054.3 linkc.331C>G p.Leu111Val missense_variant Exon 3 of 4 NP_001015054.1 P29372-5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MPGENST00000356432.8 linkc.367C>G p.Leu123Val missense_variant Exon 3 of 4 1 NM_001015052.3 ENSP00000348809.4 P29372-4
MPGENST00000219431.4 linkc.382C>G p.Leu128Val missense_variant Exon 4 of 5 3 ENSP00000219431.4 P29372-1
MPGENST00000397817.5 linkc.331C>G p.Leu111Val missense_variant Exon 3 of 4 2 ENSP00000380918.1 P29372-5
MPGENST00000436333.5 linkc.331C>G p.Leu111Val missense_variant Exon 3 of 4 2 ENSP00000388097.1 A2IDA3

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152182
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000279
AC:
7
AN:
250512
Hom.:
0
AF XY:
0.0000295
AC XY:
4
AN XY:
135496
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:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000531
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000527
AC:
77
AN:
1460788
Hom.:
0
Cov.:
32
AF XY:
0.0000592
AC XY:
43
AN XY:
726678
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000348
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000657
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152182
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74338
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.00
AC:
0
ExAC
AF:
0.0000330
AC:
4
EpiCase
AF:
0.00
EpiControl
AF:
0.000119

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 20, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.382C>G (p.L128V) alteration is located in exon 4 (coding exon 3) of the MPG gene. This alteration results from a C to G substitution at nucleotide position 382, causing the leucine (L) at amino acid position 128 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
0.086
BayesDel_addAF
Benign
-0.33
T
BayesDel_noAF
Benign
-0.58
CADD
Benign
0.28
DANN
Benign
0.96
DEOGEN2
Benign
0.016
T;.;.;T
Eigen
Benign
-0.95
Eigen_PC
Benign
-1.0
FATHMM_MKL
Benign
0.26
N
LIST_S2
Uncertain
0.89
D;T;T;T
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.24
T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.1
.;.;.;M
PrimateAI
Uncertain
0.55
T
PROVEAN
Uncertain
-2.6
D;N;N;N
REVEL
Benign
0.17
Sift
Benign
0.051
T;T;D;T
Sift4G
Uncertain
0.050
T;T;T;T
Polyphen
0.13
B;.;.;B
Vest4
0.29, 0.29, 0.26
MutPred
0.53
.;.;.;Gain of disorder (P = 0.2407);
MVP
0.26
MPC
0.057
ClinPred
0.14
T
GERP RS
-3.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.42
gMVP
0.60

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

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

Other links and lift over

dbSNP: rs774617942; hg19: chr16-133117; API