8-143429938-GGTGGTGCGCGCC-G

Position:

• chr8-143429938-GGTGGTGCGCGCC-G

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 3P and 6B. PM4 PP3 BP6_Moderate BS2

The NM_201589.4(MAFA):​c.457_468del​(p.Gly153_His156del) variant causes a inframe deletion change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00172 in 1,261,612 control chromosomes in the GnomAD database, including 3 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0040 (0 hom., cov: 29)
  • Exomes 𝑓: 0.0014 (3 hom.)
• Consequence: MAFA NM_201589.4 inframe_deletion
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 7.56

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 -3 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_201589.4.
• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP
• BP6: Variant 8-143429938-GGTGGTGCGCGCC-G is Benign according to our data. Variant chr8-143429938-GGTGGTGCGCGCC-G is described in ClinVar as [Likely_benign]. Clinvar id is 1336038.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 587 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAFA	NM_201589.4	c.457_468del	p.Gly153_His156del	inframe_deletion	1/1	ENST00000333480.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAFA	ENST00000333480.3	c.457_468del	p.Gly153_His156del	inframe_deletion	1/1		NM_201589.4	P1
MAFA	ENST00000528185.1			upstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.00398 AC: 588 AN: 147812 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.0125

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00147

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000407

Gnomad SAS AF: 0.000633

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000811

Gnomad OTH AF: 0.00148

GnomAD3 exomes AF: 0.00145 AC: 19 AN: 13136 Hom.: 0 AF XY: 0.00137 AC XY: 12 AN XY: 8732

Gnomad AFR exome AF: 0.0159

Gnomad AMR exome AF: 0.00333

Gnomad ASJ exome AF: 0.000947

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000888

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00166

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00142 AC: 1586 AN: 1113680 Hom.: 3 AF XY: 0.00133 AC XY: 716 AN XY: 536558

Gnomad4 AFR exome AF: 0.0133

Gnomad4 AMR exome AF: 0.000944

Gnomad4 ASJ exome AF: 0.000140

Gnomad4 EAS exome AF: 0.000247

Gnomad4 SAS exome AF: 0.000629

Gnomad4 FIN exome AF: 0.000208

Gnomad4 NFE exome AF: 0.00127

Gnomad4 OTH exome AF: 0.00125

GnomAD4 genome AF: 0.00397 AC: 587 AN: 147932 Hom.: 0 Cov.: 29 AF XY: 0.00400 AC XY: 288 AN XY: 72080

Gnomad4 AFR AF: 0.0124

Gnomad4 AMR AF: 0.00147

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000408

Gnomad4 SAS AF: 0.000422

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000812

Gnomad4 OTH AF: 0.00146

Alfa AF: 0.000615 Hom.: 0

Asia WGS AF: 0.000315 AC: 1 AN: 3194

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Feb 03, 2021

- -

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: rs537082716; hg19: chr8-144512108;