rs1057518878

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM1PM2PP3_ModeratePP5_Moderate

The NM_005360.5(MAF):​c.188C>G​(p.Pro63Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).

Frequency

Genomes: not found (cov: 30)

Consequence

MAF
NM_005360.5 missense

Scores

13
5
1

Clinical Significance

Likely pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 8.85
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 8 ACMG points.

PM1
In a hotspot region, there are 5 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 2 uncertain in NM_005360.5
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.893
PP5
Variant 16-79599715-G-C is Pathogenic according to our data. Variant chr16-79599715-G-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 374075.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MAFNM_005360.5 linkuse as main transcriptc.188C>G p.Pro63Arg missense_variant 1/2 ENST00000326043.5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MAFENST00000326043.5 linkuse as main transcriptc.188C>G p.Pro63Arg missense_variant 1/21 NM_005360.5 A2O75444-1
MAFENST00000569649.1 linkuse as main transcriptc.188C>G p.Pro63Arg missense_variant 1/25 P4
MAFENST00000393350.1 linkuse as main transcriptc.188C>G p.Pro63Arg missense_variant 1/1 A2O75444-2

Frequencies

GnomAD3 genomes
Cov.:
30
GnomAD4 exome
Cov.:
36
GnomAD4 genome
Cov.:
30

ClinVar

Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Developmental cataract Pathogenic:1
Likely pathogenic, criteria provided, single submitterclinical testingCentre for Mendelian Genomics, University Medical Centre LjubljanaJul 22, 2015- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
1.0
BayesDel_addAF
Pathogenic
0.31
D
BayesDel_noAF
Pathogenic
0.21
CADD
Pathogenic
32
DANN
Uncertain
0.99
DEOGEN2
Pathogenic
0.82
.;.;D
Eigen
Pathogenic
0.78
Eigen_PC
Pathogenic
0.71
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Uncertain
0.94
D;D;D
M_CAP
Pathogenic
0.98
D
MetaRNN
Pathogenic
0.89
D;D;D
MetaSVM
Pathogenic
0.84
D
MutationAssessor
Uncertain
2.4
.;M;M
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Pathogenic
0.95
D
PROVEAN
Pathogenic
-5.7
D;D;D
REVEL
Pathogenic
0.90
Sift
Pathogenic
0.0
D;D;D
Sift4G
Uncertain
0.0020
D;D;D
Polyphen
1.0
.;D;D
Vest4
0.74
MutPred
0.23
Loss of glycosylation at P63 (P = 0.0273);Loss of glycosylation at P63 (P = 0.0273);Loss of glycosylation at P63 (P = 0.0273);
MVP
1.0
ClinPred
1.0
D
GERP RS
4.1
Varity_R
0.89
gMVP
0.94

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.

Other links and lift over

dbSNP: rs1057518878; hg19: chr16-79633612; API