chr8-143430009-A-C
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PP3_StrongBS2
The NM_201589.4(MAFA):āc.398T>Gā(p.Leu133Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000019 in 1,368,528 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.00013 ( 0 hom., cov: 30)
Exomes š: 0.0000057 ( 0 hom. )
Consequence
MAFA
NM_201589.4 missense
NM_201589.4 missense
Scores
4
14
1
Clinical Significance
Conservation
PhyloP100: 6.27
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PP3
MetaRNN computational evidence supports a deleterious effect, 0.962
BS2
High AC in GnomAd4 at 19 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MAFA | NM_201589.4 | c.398T>G | p.Leu133Arg | missense_variant | 1/1 | ENST00000333480.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MAFA | ENST00000333480.3 | c.398T>G | p.Leu133Arg | missense_variant | 1/1 | NM_201589.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000127 AC: 19AN: 149362Hom.: 0 Cov.: 30
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GnomAD4 exome AF: 0.00000574 AC: 7AN: 1219166Hom.: 0 Cov.: 34 AF XY: 0.00000499 AC XY: 3AN XY: 601308
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GnomAD4 genome AF: 0.000127 AC: 19AN: 149362Hom.: 0 Cov.: 30 AF XY: 0.000151 AC XY: 11AN XY: 72760
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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 | Sep 27, 2022 | The c.398T>G (p.L133R) alteration is located in exon 1 (coding exon 1) of the MAFA gene. This alteration results from a T to G substitution at nucleotide position 398, causing the leucine (L) at amino acid position 133 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
D
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M
MutationTaster
Benign
D
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D
REVEL
Uncertain
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MutPred
Gain of disorder (P = 0.0382);
MVP
ClinPred
D
GERP RS
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at