8-143429368-C-A

Variant summary

Our verdict is Benign. The variant received -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. 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

1
4
13

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]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank MANE Protein UniProt
MAFANM_201589.4 linkc.1039G>T p.Gly347Cys missense_variant Exon 1 of 1 ENST00000333480.3 NP_963883.2 Q8NHW3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MAFAENST00000333480.3 linkc.1039G>T p.Gly347Cys missense_variant Exon 1 of 1 6 NM_201589.4 ENSP00000328364.2 Q8NHW3
MAFAENST00000528185.1 linkn.389+142G>T intron_variant Intron 1 of 1 3

Frequencies

GnomAD3 genomes
AF:
0.0459
AC:
6975
AN:
151944
Hom.:
234
Cov.:
32
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
GnomAD2 exomes
AF:
0.0573
AC:
2015
AN:
35150
AF XY:
0.0568
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 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.:
30
AF XY:
0.0676
AC XY:
41462
AN XY:
613624
show subpopulations
Gnomad4 AFR exome
AF:
0.00947
AC:
224
AN:
23658
Gnomad4 AMR exome
AF:
0.0426
AC:
447
AN:
10486
Gnomad4 ASJ exome
AF:
0.0193
AC:
370
AN:
19194
Gnomad4 EAS exome
AF:
0.0456
AC:
1239
AN:
27190
Gnomad4 SAS exome
AF:
0.0389
AC:
2330
AN:
59850
Gnomad4 FIN exome
AF:
0.0511
AC:
1660
AN:
32512
Gnomad4 NFE exome
AF:
0.0748
AC:
76284
AN:
1019854
Gnomad4 Remaining exome
AF:
0.0585
AC:
2986
AN:
51066
Heterozygous variant carriers
0
4549
9098
13647
18196
22745
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Exome Het
Exome Hom
Variant carriers
0
3018
6036
9054
12072
15090
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.0459
AC:
6973
AN:
152052
Hom.:
234
Cov.:
32
AF XY:
0.0454
AC XY:
3374
AN XY:
74360
show subpopulations
Gnomad4 AFR
AF:
0.0124
AC:
0.0124458
AN:
0.0124458
Gnomad4 AMR
AF:
0.0459
AC:
0.045853
AN:
0.045853
Gnomad4 ASJ
AF:
0.0202
AC:
0.0201729
AN:
0.0201729
Gnomad4 EAS
AF:
0.0612
AC:
0.0611847
AN:
0.0611847
Gnomad4 SAS
AF:
0.0441
AC:
0.0441176
AN:
0.0441176
Gnomad4 FIN
AF:
0.0498
AC:
0.049763
AN:
0.049763
Gnomad4 NFE
AF:
0.0660
AC:
0.0660386
AN:
0.0660386
Gnomad4 OTH
AF:
0.0479
AC:
0.0478673
AN:
0.0478673
Heterozygous variant carriers
0
350
700
1050
1400
1750
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Genome Het
Genome Hom
Variant carriers
0
80
160
240
320
400
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.0536
Hom.:
89
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
Dec 09, 2019
PreventionGenetics, part of Exact Sciences
Significance:Benign
Review Status:no assertion criteria provided
Collection Method:clinical testing

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
T
BayesDel_noAF
Uncertain
-0.070
CADD
Benign
22
DANN
Uncertain
0.99
DEOGEN2
Benign
0.19
T
Eigen
Benign
-0.32
Eigen_PC
Benign
-0.38
FATHMM_MKL
Benign
0.49
N
LIST_S2
Benign
0.46
T
MetaRNN
Benign
0.0015
T
MetaSVM
Benign
-0.33
T
MutationAssessor
Benign
0.0
N
PrimateAI
Pathogenic
0.85
D
PROVEAN
Benign
-1.3
N
REVEL
Uncertain
0.37
Sift
Uncertain
0.019
D
Sift4G
Benign
0.061
T
Polyphen
0.98
D
Vest4
0.091
ClinPred
0.016
T
GERP RS
3.0
Varity_R
0.37
gMVP
0.44
Mutation Taster
=94/6
polymorphism (auto)

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.

Other links and lift over

dbSNP: rs62521874; hg19: chr8-144511538; COSMIC: COSV61087095; API