Variant 8-143429755-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_201589.4(MAFA):c.652G>C(p.Gly218Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000289 in 1,385,116 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000029 ( 0 hom. )

Consequence

MAFA
NM_201589.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.667

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2439898).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAFA	NM_201589.4 link	c.652G>C	p.Gly218Arg	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 link	c.652G>C	p.Gly218Arg	missense_variant	1/1	6	NM_201589.4	ENSP00000328364.2		Q8NHW3
MAFA	ENST00000528185.1 link	n.144G>C		non_coding_transcript_exon_variant	1/2	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000150

AC:

AN:

133248

Hom.:

AF XY:

0.0000137

AC XY:

AN XY:

73074

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000891

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000289

AC:

AN:

1385116

Hom.:

Cov.:

AF XY:

0.00000438

AC XY:

AN XY:

684170

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000503

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 09, 2024

The c.652G>C (p.G218R) alteration is located in exon 1 (coding exon 1) of the MAFA gene. This alteration results from a G to C substitution at nucleotide position 652, causing the glycine (G) at amino acid position 218 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.63

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.25

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.21

Eigen

Benign

-0.81

Eigen_PC

Benign

-0.80

FATHMM_MKL

Benign

0.23

LIST_S2

Benign

0.54

M_CAP

Pathogenic

0.85

MetaRNN

Benign

0.24

MetaSVM

Uncertain

0.27

MutationAssessor

Benign

0.55

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-1.1

REVEL

Uncertain

0.34

Sift

Benign

0.41

Sift4G

Uncertain

0.017

Polyphen

0.72

Vest4

0.18

MutPred

0.34

Gain of methylation at G218 (P = 0.0133);

MVP

0.37

ClinPred

0.078

GERP RS

1.2

Varity_R

0.047

gMVP

0.26

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

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