8-143429783-ATGGTGGTGG-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_201589.4(MAFA):c.615_623del(p.His206_His208del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.000334 in 1,407,144 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00020 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00035 (1 hom.)
• Consequence: MAFA NM_201589.4 inframe_deletion
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 5.55

Genes affected

MAFA (HGNC:23145): (MAF bZIP transcription factor A) MAFA is a transcription factor that binds RIPE3b, a conserved enhancer element that regulates pancreatic beta cell-specific expression of the insulin gene (INS; MIM 176730) (Olbrot et al., 2002 [PubMed 12011435]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 8-143429783-ATGGTGGTGG-A is Benign according to our data. Variant chr8-143429783-ATGGTGGTGG-A is described in ClinVar as [Likely_benign]. Clinvar id is 2443167.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 29 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAFA	NM_201589.4	c.615_623del	p.His206_His208del	inframe_deletion	1/1	ENST00000333480.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAFA	ENST00000333480.3	c.615_623del	p.His206_His208del	inframe_deletion	1/1		NM_201589.4	P1
MAFA	ENST00000528185.1	n.107_115del		non_coding_transcript_exon_variant	1/2	3

Frequencies

GnomAD3 genomes AF: 0.000197 AC: 29 AN: 146948 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000752

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000671

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000861

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000301

Gnomad OTH AF: 0.000493

GnomAD3 exomes AF: 0.000558 AC: 38 AN: 68082 Hom.: 0 AF XY: 0.000617 AC XY: 23 AN XY: 37262

Gnomad AFR exome AF: 0.000457

Gnomad AMR exome AF: 0.000362

Gnomad ASJ exome AF: 0.000667

Gnomad EAS exome AF: 0.00146

Gnomad SAS exome AF: 0.0000872

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000804

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000350 AC: 441 AN: 1260076 Hom.: 1 AF XY: 0.000354 AC XY: 219 AN XY: 619322

Gnomad4 AFR exome AF: 0.000404

Gnomad4 AMR exome AF: 0.000464

Gnomad4 ASJ exome AF: 0.000223

Gnomad4 EAS exome AF: 0.000409

Gnomad4 SAS exome AF: 0.000230

Gnomad4 FIN exome AF: 0.0000329

Gnomad4 NFE exome AF: 0.000357

Gnomad4 OTH exome AF: 0.000514

GnomAD4 genome AF: 0.000197 AC: 29 AN: 147068 Hom.: 0 Cov.: 0 AF XY: 0.000167 AC XY: 12 AN XY: 71674

Gnomad4 AFR AF: 0.0000749

Gnomad4 AMR AF: 0.0000670

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000864

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000301

Gnomad4 OTH AF: 0.000488

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, no assertion criteria provided

clinical testing

Genetic Services Laboratory, University of Chicago

Jun 09, 2022

- -

MAFA-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 28, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs141816879; hg19: chr8-144511953;