Variant 16-85592-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001015052.3(MPG):c.697C>A(p.Gln233Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000959 in 1,459,856 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 34)

Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

MPG
NM_001015052.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.165

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:

NPRL3 (HGNC:14124): (NPR3 like, GATOR1 complex subunit) Contributes to GTPase activator activity. Involved in cellular response to amino acid starvation and negative regulation of TOR signaling. Located in lysosomal membrane. Part of GATOR1 complex. Implicated in focal epilepsy. [provided by Alliance of Genome Resources, Apr 2022]

NPRL3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.04661256).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MPG	NM_001015052.3 linkuse as main transcript	c.697C>A	p.Gln233Lys	missense_variant	4/4	ENST00000356432.8
NPRL3	NM_001077350.3 linkuse as main transcript	c.*1113G>T		3_prime_UTR_variant	14/14	ENST00000611875.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MPG	ENST00000356432.8 linkuse as main transcript	c.697C>A	p.Gln233Lys	missense_variant	4/4	1	NM_001015052.3	P2	P29372-4
NPRL3	ENST00000611875.5 linkuse as main transcript	c.*1113G>T		3_prime_UTR_variant	14/14	5	NM_001077350.3	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000805

AC:

AN:

248318

Hom.:

AF XY:

0.00000743

AC XY:

AN XY:

134658

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000582

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000959

AC:

AN:

1459856

Hom.:

Cov.:

AF XY:

0.00000826

AC XY:

AN XY:

726012

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

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:

0.0000108

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

Dec 20, 2023

The c.712C>A (p.Q238K) alteration is located in exon 5 (coding exon 4) of the MPG gene. This alteration results from a C to A substitution at nucleotide position 712, causing the glutamine (Q) at amino acid position 238 to be replaced by a lysine (K). 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

0.068

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.74

Cadd

Benign

0.26

Dann

Benign

0.52

DEOGEN2

Benign

0.010

T;.;.;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.077

LIST_S2

Benign

0.75

T;T;T;T

M_CAP

Benign

0.0048

MetaRNN

Benign

0.047

T;T;T;T

MetaSVM

Benign

-0.96

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.84

N;N;N;N

REVEL

Benign

0.024

Sift

Benign

0.65

T;T;T;T

Sift4G

Benign

0.96

T;T;T;T

Polyphen

0.0

.;.;.;B

Vest4

0.086, 0.085, 0.082

MutPred

0.41

.;.;.;Gain of ubiquitination at Q238 (P = 0.0104);

MVP

0.27

MPC

0.064

ClinPred

0.014

GERP RS

0.47

Varity_R

0.14

gMVP

0.50

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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