Variant 8-143429368-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_201589.4(MAFA):c.1039G>T(p.Gly347Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0662 in 1,399,650 control chromosomes in the GnomAD database, including 3,387 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.046 ( 234 hom., cov: 32)

Exomes 𝑓: 0.069 ( 3153 hom. )

Consequence

MAFA
NM_201589.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.647

Variant links:

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]

MAFA links:

MAFA (HGNC:):

MAFA links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0014564693).

BP6

Variant 8-143429368-C-A is Benign according to our data. Variant chr8-143429368-C-A is described in ClinVar as [Benign]. Clinvar id is 3055993.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0644 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAFA	NM_201589.4 linkuse as main transcript	c.1039G>T	p.Gly347Cys	missense_variant	1/1	ENST00000333480.3	NP_963883.2	Q8NHW3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAFA	ENST00000333480.3 linkuse as main transcript	c.1039G>T	p.Gly347Cys	missense_variant	1/1	6	NM_201589.4	ENSP00000328364.2		Q8NHW3
MAFA	ENST00000528185.1 linkuse as main transcript	n.389+142G>T		intron_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0459

AC:

6975

AN:

151944

Hom.:

234

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0125

Gnomad AMI

AF:

0.0471

Gnomad AMR

AF:

0.0459

Gnomad ASJ

AF:

0.0202

Gnomad EAS

AF:

0.0610

Gnomad SAS

AF:

0.0443

Gnomad FIN

AF:

0.0498

Gnomad MID

AF:

0.00955

Gnomad NFE

AF:

0.0660

Gnomad OTH

AF:

0.0489

GnomAD3 exomes

AF:

0.0573

AC:

2015

AN:

35150

Hom.:

AF XY:

0.0568

AC XY:

1264

AN XY:

22234

show subpopulations

Gnomad AFR exome

AF:

0.0118

Gnomad AMR exome

AF:

0.0499

Gnomad ASJ exome

AF:

0.0219

Gnomad EAS exome

AF:

0.0846

Gnomad SAS exome

AF:

0.0455

Gnomad FIN exome

AF:

0.0576

Gnomad NFE exome

AF:

0.0709

Gnomad OTH exome

AF:

0.0568

GnomAD4 exome

AF:

0.0686

AC:

85626

AN:

1247598

Hom.:

3153

Cov.:

AF XY:

0.0676

AC XY:

41462

AN XY:

613624

show subpopulations

Gnomad4 AFR exome

AF:

0.00947

Gnomad4 AMR exome

AF:

0.0426

Gnomad4 ASJ exome

AF:

0.0193

Gnomad4 EAS exome

AF:

0.0456

Gnomad4 SAS exome

AF:

0.0389

Gnomad4 FIN exome

AF:

0.0511

Gnomad4 NFE exome

AF:

0.0748

Gnomad4 OTH exome

AF:

0.0585

GnomAD4 genome

AF:

0.0459

AC:

6973

AN:

152052

Hom.:

234

Cov.:

AF XY:

0.0454

AC XY:

3374

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.0124

Gnomad4 AMR

AF:

0.0459

Gnomad4 ASJ

AF:

0.0202

Gnomad4 EAS

AF:

0.0612

Gnomad4 SAS

AF:

0.0441

Gnomad4 FIN

AF:

0.0498

Gnomad4 NFE

AF:

0.0660

Gnomad4 OTH

AF:

0.0479

Alfa

AF:

0.0547

Hom.:

Bravo

AF:

0.0443

TwinsUK

AF:

0.0731

AC:

271

ALSPAC

AF:

0.0807

AC:

311

ExAC

AF:

0.0309

AC:

1440

Asia WGS

AF:

0.0560

AC:

195

AN:

3438

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

MAFA-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 09, 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

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Uncertain

-0.070

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.19

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.38

FATHMM_MKL

Benign

0.49

LIST_S2

Benign

0.46

MetaRNN

Benign

0.0015

MetaSVM

Benign

-0.33

MutationAssessor

Benign

0.0

MutationTaster

Benign

0.87

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-1.3

REVEL

Uncertain

0.37

Sift

Uncertain

0.019

Sift4G

Benign

0.061

Polyphen

0.98

Vest4

0.091

ClinPred

0.016

GERP RS

3.0

Varity_R

0.37

gMVP

0.44

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over