chr16-79594540-G-A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 1P and 2B. PP2BP4_Moderate

The NM_005360.5(MAF):​c.1132C>T​(p.Arg378Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000064 in 1,562,532 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R378S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000064 ( 0 hom. )

Consequence

MAF
NM_005360.5 missense

Scores

1
3
12

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.272

Publications

0 publications found
Variant links:
Genes affected
MAF (HGNC:6776): (MAF bZIP transcription factor) The protein encoded by this gene is a DNA-binding, leucine zipper-containing transcription factor that acts as a homodimer or as a heterodimer. Depending on the binding site and binding partner, the encoded protein can be a transcriptional activator or repressor. This protein plays a role in the regulation of several cellular processes, including embryonic lens fiber cell development, increased T-cell susceptibility to apoptosis, and chondrocyte terminal differentiation. Defects in this gene are a cause of juvenile-onset pulverulent cataract as well as congenital cerulean cataract 4 (CCA4). Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2010]
MAF Gene-Disease associations (from GenCC):
  • Ayme-Gripp syndrome
    Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
  • cataract 21 multiple types
    Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Ambry Genetics
  • cataract - microcornea syndrome
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • cerulean cataract
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • pulverulent cataract
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • Fine-Lubinsky syndrome
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

PP2
Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 22 curated pathogenic missense variants (we use a threshold of 10). The gene has 7 curated benign missense variants. Gene score misZ: 1.1779 (below the threshold of 3.09). Trascript score misZ: -0.24854 (below the threshold of 3.09). GenCC associations: The gene is linked to cerulean cataract, Fine-Lubinsky syndrome, cataract 21 multiple types, Ayme-Gripp syndrome, pulverulent cataract, cataract - microcornea syndrome.
BP4
Computational evidence support a benign effect (MetaRNN=0.07454589).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MAFNM_005360.5 linkc.1132C>T p.Arg378Cys missense_variant Exon 2 of 2 ENST00000326043.5 NP_005351.2 O75444-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MAFENST00000326043.5 linkc.1132C>T p.Arg378Cys missense_variant Exon 2 of 2 1 NM_005360.5 ENSP00000327048.4 O75444-1
MAFENST00000393350.1 linkc.*4241C>T 3_prime_UTR_variant Exon 1 of 1 6 ENSP00000377019.1 O75444-2
MAFENST00000569649.1 linkc.1118+4245C>T intron_variant Intron 1 of 1 5 ENSP00000455097.1 H3BP11

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
152038
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.0000229
AC:
4
AN:
174998
AF XY:
0.0000324
show subpopulations
Gnomad AFR exome
AF:
0.0000939
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000427
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000638
AC:
9
AN:
1410494
Hom.:
0
Cov.:
31
AF XY:
0.00000574
AC XY:
4
AN XY:
696484
show subpopulations
African (AFR)
AF:
0.000124
AC:
4
AN:
32294
American (AMR)
AF:
0.00
AC:
0
AN:
38018
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25454
East Asian (EAS)
AF:
0.00
AC:
0
AN:
37288
South Asian (SAS)
AF:
0.00
AC:
0
AN:
80144
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
50074
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5714
European-Non Finnish (NFE)
AF:
0.00000462
AC:
5
AN:
1083108
Other (OTH)
AF:
0.00
AC:
0
AN:
58400
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.481
Heterozygous variant carriers
0
1
2
2
3
4
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<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:
0.00000658
AC:
1
AN:
152038
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74228
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
41386
American (AMR)
AF:
0.00
AC:
0
AN:
15270
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3472
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5192
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4820
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10552
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
0.0000147
AC:
1
AN:
68030
Other (OTH)
AF:
0.00
AC:
0
AN:
2090
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<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:
0.00
Hom.:
0
Bravo
AF:
0.00000756
ExAC
AF:
0.00000859
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.18
T
BayesDel_noAF
Benign
-0.28
CADD
Benign
16
DANN
Benign
0.95
Eigen
Benign
-0.50
Eigen_PC
Benign
-0.46
FATHMM_MKL
Benign
0.34
N
LIST_S2
Benign
0.54
T
M_CAP
Uncertain
0.27
D
MetaRNN
Benign
0.075
T
MetaSVM
Uncertain
-0.15
T
PhyloP100
-0.27
PrimateAI
Benign
0.22
T
PROVEAN
Benign
-0.58
N
REVEL
Uncertain
0.32
Sift
Pathogenic
0.0
D
Sift4G
Benign
0.24
T
Polyphen
0.0010
B
Vest4
0.12
MutPred
0.26
Loss of helix (P = 0.0237);
MVP
0.91
ClinPred
0.78
D
GERP RS
-4.2
gMVP
0.18
Mutation Taster
=98/2
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.11
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs752338390; hg19: chr16-79628437; API