NM_002359.4:c.333C>T

Variant names:

• chr17-81922761-G-A
• rs143241856
• NM_002359.4:c.333C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_002359.4(MAFG):​c.333C>T​(p.Tyr111Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000291 in 1,593,358 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00035 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00029 (1 hom.)
• Consequence: MAFG NM_002359.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.770
• Publications: 1 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: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP6: Variant 17-81922761-G-A is Benign according to our data. Variant chr17-81922761-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3387959.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.77 with no splicing effect.
• BS2: High AC in GnomAd4 at 53 AD gene.

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.333C>T	p.Tyr111Tyr	synonymous	Exon 3 of 3	NP_002350.1	O15525
	MAFG	NM_032711.4		c.333C>T	p.Tyr111Tyr	synonymous	Exon 3 of 3	NP_116100.2
	MAFG-AS1	NR_186500.1		n.-138G>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.333C>T	p.Tyr111Tyr	synonymous	Exon 3 of 3	ENSP00000350369.4	O15525
	MAFG	ENST00000392366.7	TSL:1	c.333C>T	p.Tyr111Tyr	synonymous	Exon 3 of 3	ENSP00000376173.3	O15525
	MAFG	ENST00000899697.1		c.333C>T	p.Tyr111Tyr	synonymous	Exon 3 of 3	ENSP00000569756.1

Frequencies

GnomAD3 genomes AF: 0.000348 AC: 53 AN: 152194 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00151

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000500

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000411 AC: 88 AN: 214366 AF XY: 0.000430

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000613

Gnomad FIN exome AF: 0.00178

Gnomad NFE exome AF: 0.000537

Gnomad OTH exome AF: 0.000552

GnomAD4 exome AF: 0.000285 AC: 411 AN: 1441164 Hom.: 1 Cov.: 32 AF XY: 0.000312 AC XY: 223 AN XY: 714790

African (AFR) AF: 0.0000301 AC: 1 AN: 33234

American (AMR) AF: 0.00 AC: 0 AN: 42168

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25650

East Asian (EAS) AF: 0.000103 AC: 4 AN: 38898

South Asian (SAS) AF: 0.0000120 AC: 1 AN: 83462

European-Finnish (FIN) AF: 0.00168 AC: 85 AN: 50706

Middle Eastern (MID) AF: 0.000177 AC: 1 AN: 5656

European-Non Finnish (NFE) AF: 0.000274 AC: 302 AN: 1101878

Other (OTH) AF: 0.000286 AC: 17 AN: 59512

GnomAD4 genome AF: 0.000348 AC: 53 AN: 152194 Hom.: 0 Cov.: 32 AF XY: 0.000390 AC XY: 29 AN XY: 74352

African (AFR) AF: 0.00 AC: 0 AN: 41456

American (AMR) AF: 0.000131 AC: 2 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00151 AC: 16 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.000500 AC: 34 AN: 68014

Other (OTH) AF: 0.000478 AC: 1 AN: 2090

Alfa AF: 0.000480 Hom.: 0

Bravo AF: 0.000234

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	5.1
DANN	Benign	0.94
PhyloP100		-0.77
Mutation Taster		=100/0	polymorphism

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: rs143241856; hg19: chr17-79880637;