8-143430014-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_201589.4(MAFA):c.393C>T(p.Leu131=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00526 in 1,373,712 control chromosomes in the GnomAD database, including 285 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.027 (172 hom., cov: 30)
  • Exomes 𝑓: 0.0026 (113 hom.)
• Consequence: MAFA NM_201589.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.08

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 Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 8-143430014-G-A is Benign according to our data. Variant chr8-143430014-G-A is described in ClinVar as [Benign]. Clinvar id is 3056164.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.08 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0898 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAFA	NM_201589.4	c.393C>T	p.Leu131=	synonymous_variant	1/1	ENST00000333480.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAFA	ENST00000333480.3	c.393C>T	p.Leu131=	synonymous_variant	1/1		NM_201589.4	P1

Frequencies

GnomAD3 genomes AF: 0.0271 AC: 4042 AN: 149358 Hom.: 171 Cov.: 30

Gnomad AFR AF: 0.0922

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0126

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000284

Gnomad OTH AF: 0.0211

GnomAD3 exomes AF: 0.00415 AC: 386 AN: 93000 Hom.: 12 AF XY: 0.00268 AC XY: 145 AN XY: 54030

Gnomad AFR exome AF: 0.0877

Gnomad AMR exome AF: 0.00542

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000121

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000329

Gnomad OTH exome AF: 0.00515

GnomAD4 exome AF: 0.00259 AC: 3174 AN: 1224246 Hom.: 113 Cov.: 34 AF XY: 0.00230 AC XY: 1390 AN XY: 604170

Gnomad4 AFR exome AF: 0.0908

Gnomad4 AMR exome AF: 0.00726

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000166

Gnomad4 FIN exome AF: 0.0000301

Gnomad4 NFE exome AF: 0.000469

Gnomad4 OTH exome AF: 0.00609

GnomAD4 genome AF: 0.0271 AC: 4053 AN: 149466 Hom.: 172 Cov.: 30 AF XY: 0.0263 AC XY: 1918 AN XY: 72880

Gnomad4 AFR AF: 0.0923

Gnomad4 AMR AF: 0.0126

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000284

Gnomad4 OTH AF: 0.0208

Alfa AF: 0.0192 Hom.: 12

Bravo AF: 0.0301

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

MAFA-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 06, 2019

This variant is classified as 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

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
Cadd	Benign	9.6
Dann	Uncertain	0.98

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

Publications

LitVar

Other links and lift over

dbSNP: rs75183115; hg19: chr8-144512184;