17-81922673-C-A

Variant names:

• chr17-81922673-C-A
• rs774502626
• NM_002359.4:c.421G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002359.4(MAFG):​c.421G>T​(p.Val141Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000738 in 1,354,626 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V141I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
• Consequence: MAFG NM_002359.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.10
• Publications: 0 publications found

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-AS1 (HGNC:56705): (MAFG antisense RNA 1)

ENSG00000293667 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20120472).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002359.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAFG	NM_002359.4	MANE Select	c.421G>T	p.Val141Phe	missense	Exon 3 of 3	NP_002350.1	O15525
	MAFG	NM_032711.4		c.421G>T	p.Val141Phe	missense	Exon 3 of 3	NP_116100.2
	MAFG-AS1	NR_186500.1		n.-226C>A		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAFG	ENST00000357736.9	TSL:1 MANE Select	c.421G>T	p.Val141Phe	missense	Exon 3 of 3	ENSP00000350369.4	O15525
	MAFG	ENST00000392366.7	TSL:1	c.421G>T	p.Val141Phe	missense	Exon 3 of 3	ENSP00000376173.3	O15525
	MAFG	ENST00000899697.1		c.421G>T	p.Val141Phe	missense	Exon 3 of 3	ENSP00000569756.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000142 AC: 2 AN: 140494 AF XY: 0.0000133

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000294

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.38e-7 AC: 1 AN: 1354626 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 664888

African (AFR) AF: 0.00 AC: 0 AN: 29328

American (AMR) AF: 0.00 AC: 0 AN: 25328

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19702

East Asian (EAS) AF: 0.00 AC: 0 AN: 37616

South Asian (SAS) AF: 0.00 AC: 0 AN: 69136

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47678

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5290

European-Non Finnish (NFE) AF: 9.39e-7 AC: 1 AN: 1065066

Other (OTH) AF: 0.00 AC: 0 AN: 55482

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Uncertain	0.055	T
BayesDel_noAF	Benign	-0.16
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.086	T
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.035
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.97	D
M_CAP	Uncertain	0.098	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.55	T
MutationAssessor	Benign	1.4	L
PhyloP100		1.1
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-0.29	N
REVEL	Benign	0.24
Sift	Uncertain	0.014	D
Sift4G	Uncertain	0.023	D
Polyphen		0.20	B
Vest4		0.36
MutPred		0.32		Gain of sheet (P = 0.0149)
MVP		0.76
MPC		1.3
ClinPred		0.42	T
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.13
gMVP		0.56

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

Other links and lift over

dbSNP: rs774502626; hg19: chr17-79880549;