chr22-38214461-C-A
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_012323.4(MAFF):c.78C>A(p.Asp26Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000529 in 1,608,186 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 (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000058 ( 0 hom. )
Consequence
MAFF
NM_012323.4 missense
NM_012323.4 missense
Scores
6
9
3
Clinical Significance
Conservation
PhyloP100: 1.57
Genes affected
MAFF (HGNC:6780): (MAF bZIP transcription factor F) The protein encoded by this gene is a basic leucine zipper (bZIP) transcription factor that lacks a transactivation domain. It is known to bind the US-2 DNA element in the promoter of the oxytocin receptor (OTR) gene and most likely heterodimerizes with other leucine zipper-containing proteins to enhance expression of the OTR gene during term pregnancy. The encoded protein can also form homodimers, and since it lacks a transactivation domain, the homodimer may act as a repressor of transcription. This gene may also be involved in the cellular stress response. Multiple transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jun 2009]
PLA2G6 (HGNC:9039): (phospholipase A2 group VI) The protein encoded by this gene is an A2 phospholipase, a class of enzyme that catalyzes the release of fatty acids from phospholipids. The encoded protein may play a role in phospholipid remodelling, arachidonic acid release, leukotriene and prostaglandin synthesis, fas-mediated apoptosis, and transmembrane ion flux in glucose-stimulated B-cells. Several transcript variants encoding multiple isoforms have been described, but the full-length nature of only three of them have been determined to date. [provided by RefSeq, Dec 2010]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.932
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MAFF | NM_012323.4 | c.78C>A | p.Asp26Glu | missense_variant | 3/3 | ENST00000338483.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MAFF | ENST00000338483.7 | c.78C>A | p.Asp26Glu | missense_variant | 3/3 | 1 | NM_012323.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152238Hom.: 0 Cov.: 32
GnomAD3 genomes
AF:
AC:
1
AN:
152238
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.00000837 AC: 2AN: 238936Hom.: 0 AF XY: 0.00000763 AC XY: 1AN XY: 131126
GnomAD3 exomes
AF:
AC:
2
AN:
238936
Hom.:
AF XY:
AC XY:
1
AN XY:
131126
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000577 AC: 84AN: 1455948Hom.: 0 Cov.: 32 AF XY: 0.0000511 AC XY: 37AN XY: 724174
GnomAD4 exome
AF:
AC:
84
AN:
1455948
Hom.:
Cov.:
32
AF XY:
AC XY:
37
AN XY:
724174
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152238Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74374
GnomAD4 genome
AF:
AC:
1
AN:
152238
Hom.:
Cov.:
32
AF XY:
AC XY:
0
AN XY:
74374
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Bravo
AF:
ExAC
AF:
AC:
1
EpiCase
AF:
EpiControl
AF:
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 | Jul 17, 2023 | The c.78C>A (p.D26E) alteration is located in exon 3 (coding exon 2) of the MAFF gene. This alteration results from a C to A substitution at nucleotide position 78, causing the aspartic acid (D) at amino acid position 26 to be replaced by a glutamic acid (E). 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
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Pathogenic
D;D;D;D;D
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M;M;.;M;M
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D;D;D
REVEL
Pathogenic
Sift
Benign
T;T;D;T;T
Sift4G
Uncertain
D;D;T;D;D
Polyphen
D;D;.;D;D
Vest4
MutPred
Loss of catalytic residue at D26 (P = 0.0891);Loss of catalytic residue at D26 (P = 0.0891);Loss of catalytic residue at D26 (P = 0.0891);Loss of catalytic residue at D26 (P = 0.0891);Loss of catalytic residue at D26 (P = 0.0891);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at