GeneBe

16-79594503-C-T

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PVS1_ModeratePM2

The NM_005360.5(MAF):​c.1169G>A​(p.Trp390*) variant causes a stop gained change involving the alteration of a non-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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

MAF
NM_005360.5 stop_gained

Scores

2
4
1

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.03

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: Uncertain_significance. The variant received 4 ACMG points.

PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0355 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MAFNM_005360.5 linkc.1169G>A p.Trp390* stop_gained 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.1169G>A p.Trp390* stop_gained Exon 2 of 2 1 NM_005360.5 ENSP00000327048.4 O75444-1
MAFENST00000393350.1 linkc.*4278G>A 3_prime_UTR_variant Exon 1 of 1 6 ENSP00000377019.1 O75444-2
MAFENST00000569649.1 linkc.1118+4282G>A intron_variant Intron 1 of 1 5 ENSP00000455097.1 H3BP11

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1415266
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
699328
African (AFR)
AF:
0.00
AC:
0
AN:
32492
American (AMR)
AF:
0.00
AC:
0
AN:
38966
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25502
East Asian (EAS)
AF:
0.00
AC:
0
AN:
37812
South Asian (SAS)
AF:
0.00
AC:
0
AN:
80542
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
50400
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5720
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1085314
Other (OTH)
AF:
0.00
AC:
0
AN:
58518
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
Feb 06, 2024
GeneDx
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

Nonsense variant predicted to result in protein truncation as the last 14 amino acids are lost, although loss-of-function variants have not been reported downstream of this position in the protein; Not observed at significant frequency in large population cohorts (gnomAD); Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.56
D
BayesDel_noAF
Pathogenic
0.57
CADD
Pathogenic
39
DANN
Uncertain
0.99
Eigen
Uncertain
0.64
Eigen_PC
Uncertain
0.49
FATHMM_MKL
Uncertain
0.81
D
PhyloP100
2.0
Vest4
0.42
GERP RS
3.6

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.23
Details are displayed if max score is > 0.2
DS_AL_spliceai
0.23
Position offset: 50

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

Publications

Other links and lift over

hg19: chr16-79628400; API