17-81922612-C-G

Variant names:

• chr17-81922612-C-G
• NM_002359.4:c.482G>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_002359.4(MAFG):​c.482G>C​(p.Arg161Pro) 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. 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: 5.69

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]

ACMG classification

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=0.32182395).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAFG	NM_002359.4	c.482G>C	p.Arg161Pro	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.482G>C	p.Arg161Pro	missense_variant	Exon 3 of 3	1	NM_002359.4	ENSP00000350369.4
MAFG	ENST00000392366.7	c.482G>C	p.Arg161Pro	missense_variant	Exon 3 of 3	1		ENSP00000376173.3
MAFG	ENST00000574686.1	c.*186G>C		downstream_gene_variant		5		ENSP00000459634.1

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

Oct 16, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.482G>C (p.R161P) alteration is located in exon 3 (coding exon 2) of the MAFG gene. This alteration results from a G to C substitution at nucleotide position 482, causing the arginine (R) at amino acid position 161 to be replaced by a proline (P). 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	0.31
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.030
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.088	T;T
Eigen	Benign	-0.029
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.93	.;D
M_CAP	Benign	0.062	D
MetaRNN	Benign	0.32	T;T
MetaSVM	Benign	-0.35	T
MutationAssessor	Uncertain	2.0	M;M
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-0.76	N;N
REVEL	Uncertain	0.41
Sift	Uncertain	0.0060	D;D
Sift4G	Benign	0.14	T;T
Polyphen		0.31	B;B
Vest4		0.57
MutPred		0.35		Loss of MoRF binding (P = 0);Loss of MoRF binding (P = 0);
MVP		0.82
MPC		1.4
ClinPred		0.73	D
GERP RS		4.4
Varity_R		0.30
gMVP		0.83

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: chr17-79880488;