17-81922769-A-C

Variant names:

• chr17-81922769-A-C
• NM_002359.4:c.325T>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002359.4(MAFG):​c.325T>G​(p.Ser109Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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 (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MAFG NM_002359.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.97

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]

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

ACMG classification

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=0.22775981).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAFG	NM_002359.4	c.325T>G	p.Ser109Ala	missense_variant	Exon 3 of 3	ENST00000357736.9	NP_002350.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAFG	ENST00000357736.9	c.325T>G	p.Ser109Ala	missense_variant	Exon 3 of 3	1	NM_002359.4	ENSP00000350369.4
MAFG	ENST00000392366.7	c.325T>G	p.Ser109Ala	missense_variant	Exon 3 of 3	1		ENSP00000376173.3
MAFG	ENST00000574686.1	c.*29T>G		downstream_gene_variant		5		ENSP00000459634.1
ENSG00000264769	ENST00000580897.1	n.-130A>C		upstream_gene_variant		4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 20, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.325T>G (p.S109A) alteration is located in exon 3 (coding exon 2) of the MAFG gene. This alteration results from a T to G substitution at nucleotide position 325, causing the serine (S) at amino acid position 109 to be replaced by an alanine (A). 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	0.061
BayesDel_addAF	Uncertain	0.066	T
BayesDel_noAF	Benign	-0.14
CADD	Benign	20
DANN	Benign	0.84
DEOGEN2	Uncertain	0.44	T;T
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.19
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.47	.;T
M_CAP	Benign	0.048	D
MetaRNN	Benign	0.23	T;T
MetaSVM	Benign	-0.61	T
MutationAssessor	Benign	-0.69	N;N
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	-0.78	N;N
REVEL	Uncertain	0.30
Sift	Benign	0.80	T;T
Sift4G	Benign	0.92	T;T
Polyphen		0.0070	B;B
Vest4		0.30
MutPred		0.40		Loss of phosphorylation at S109 (P = 0.0433);Loss of phosphorylation at S109 (P = 0.0433);
MVP		0.76
MPC		0.71
ClinPred		0.93	D
GERP RS		4.2
Varity_R		0.22
gMVP		0.64

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-79880645;