rs879255275

Variant names:

• chr20-40688047-AT-A
• rs879255275
• NM_005461.5:c.803delA

Variant summary

Our verdict is Likely pathogenic. The variant received 8 ACMG points: 8P and 0B. PVS1_Strong PM2 PP5_Moderate

The NM_005461.5(MAFB):​c.803delA​(p.Asn268MetfsTer125) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: MAFB NM_005461.5 frameshift
• Clinical Significance: Pathogenic criteria provided, single submitter P:2
• Conservation: PhyloP100: 3.39
• Publications: 1 publications found

Genes affected

MAFB (HGNC:6408): (MAF bZIP transcription factor B) The protein encoded by this gene is a basic leucine zipper (bZIP) transcription factor that plays an important role in the regulation of lineage-specific hematopoiesis. The encoded nuclear protein represses ETS1-mediated transcription of erythroid-specific genes in myeloid cells. This gene contains no introns. [provided by RefSeq, Jul 2008]

MAFB Gene-Disease associations (from GenCC):

• multicentric carpo-tarsal osteolysis with or without nephropathy

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet
• Duane retraction syndrome

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: G2P, Orphanet
• Duane retraction syndrome 3 with or without deafness

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Likely_pathogenic. The variant received 8 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.174 CDS is truncated, and there are 1 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 20-40688047-AT-A is Pathogenic according to our data. Variant chr20-40688047-AT-A is described in ClinVar as Pathogenic. ClinVar VariationId is 224628.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005461.5. 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
	MAFB	NM_005461.5	MANE Select	c.803delA	p.Asn268MetfsTer125	frameshift	Exon 1 of 1	NP_005452.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAFB	ENST00000373313.3	TSL:6 MANE Select	c.803delA	p.Asn268MetfsTer125	frameshift	Exon 1 of 1	ENSP00000362410.2	Q9Y5Q3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
1	-	-	Duane retraction syndrome 2;C0994516:Duane syndrome type 1 (1)
1	-	-	Duane retraction syndrome 3 with or without deafness (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.4
Mutation Taster		=2/198	disease causing (ClinVar)

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: rs879255275; hg19: chr20-39316687;