17-81922688-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_002359.4(MAFG):c.406G>A(p.Gly136Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000119 in 1,507,646 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: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

MAFG
NM_002359.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.716

Variant links:

Genes affected

MAFG (HGNC:6781): (MAF bZIP transcription factor G) Globin gene expression is regulated through nuclear factor erythroid-2 (NFE2) elements located in enhancer-like locus control regions positioned many kb upstream of alpha- and beta-gene clusters (summarized by Blank et al., 1997 [PubMed 9166829]). NFE2 DNA-binding activity consists of a heterodimer containing a ubiquitous small Maf protein (MafF, MIM 604877; MafG; or MafK, MIM 600197) and the tissue-restricted protein p45 NFE2 (MIM 601490). Both subunits are members of the activator protein-1-like superfamily of basic leucine zipper (bZIP) proteins (see MIM 165160).[supplied by OMIM, Mar 2010]

MAFG links:

ENSG00000264769 (HGNC:56705): (MAFG antisense RNA 1)

ENSG00000264769 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0372656).

BS2

High AC in GnomAdExome4 at 16 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAFG	NM_002359.4 link	c.406G>A	p.Gly136Ser	missense_variant	Exon 3 of 3	ENST00000357736.9	NP_002350.1	O15525A0A024R8X1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MAFG	ENST00000357736.9 link	c.406G>A	p.Gly136Ser	missense_variant	Exon 3 of 3	1	NM_002359.4	ENSP00000350369.4	O15525
MAFG	ENST00000392366.7 link	c.406G>A	p.Gly136Ser	missense_variant	Exon 3 of 3	1		ENSP00000376173.3	O15525
MAFG	ENST00000574686.1 link	c.*110G>A		downstream_gene_variant		5		ENSP00000459634.1	I3L2F8
ENSG00000264769	ENST00000580897.1 link	n.-211C>T		upstream_gene_variant		4

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000453

AC:

AN:

132436

Hom.:

AF XY:

0.0000419

AC XY:

AN XY:

71588

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000265

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:

0.0000162

Gnomad OTH exome

AF:

0.000324

GnomAD4 exome

AF:

0.0000118

AC:

AN:

1355468

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

665864

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000164

Gnomad4 ASJ exome

AF:

0.0000491

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000142

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000751

Gnomad4 OTH exome

AF:

0.0000180

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152178

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000264

ExAC

AF:

0.0000428

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 04, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.406G>A (p.G136S) alteration is located in exon 3 (coding exon 2) of the MAFG gene. This alteration results from a G to A substitution at nucleotide position 406, causing the glycine (G) at amino acid position 136 to be replaced by a serine (S). 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

0.070

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.10

T;T

Eigen

Benign

-0.99

Eigen_PC

Benign

-0.85

FATHMM_MKL

Benign

0.64

LIST_S2

Benign

0.80

.;T

M_CAP

Benign

0.027

MetaRNN

Benign

0.037

T;T

MetaSVM

Benign

-0.87

MutationAssessor

Benign

0.20

N;N

PrimateAI

Uncertain

0.58

PROVEAN

Benign

0.42

N;N

REVEL

Benign

0.15

Sift

Benign

0.85

T;T

Sift4G

Benign

0.49

T;T

Polyphen

0.0

B;B

Vest4

0.10

MutPred

0.20

Gain of glycosylation at G136 (P = 0.0179);Gain of glycosylation at G136 (P = 0.0179);

MVP

0.35

MPC

0.84

ClinPred

0.031

GERP RS

-1.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.3

Varity_R

0.060

gMVP

0.63

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.

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