Genetic Variant MAFF:p.Ala113Glu (chr22-38214721-C-A) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_012323.4(MAFF):c.338C>A(p.Ala113Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000602 in 1,496,126 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

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

Exomes 𝑓: 0.0000060 ( 0 hom. )

Consequence

MAFF
NM_012323.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.41

Variant links:

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]

MAFF links:

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]

PLA2G6 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.793

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAFF	NM_012323.4 link	c.338C>A	p.Ala113Glu	missense_variant	Exon 3 of 3	ENST00000338483.7	NP_036455.1	Q9ULX9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAFF	ENST00000338483.7 link	c.338C>A	p.Ala113Glu	missense_variant	Exon 3 of 3	1	NM_012323.4	ENSP00000345393.2		Q9ULX9-1

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

151874

Hom.:

Cov.:

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

GnomAD4 exome

AF:

0.00000595

AC:

AN:

1344252

Hom.:

Cov.:

AF XY:

0.00000453

AC XY:

AN XY:

662364

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000257

Gnomad4 NFE exome

AF:

0.00000660

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000658

AC:

AN:

151874

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74172

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.84

BayesDel_addAF

Pathogenic

0.23

BayesDel_noAF

Uncertain

0.090

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.74

D;.;D;D;D;D;D

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.48

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.94

.;D;D;D;D;.;.

M_CAP

Pathogenic

0.83

MetaRNN

Pathogenic

0.79

D;D;D;D;D;D;D

MetaSVM

Uncertain

0.70

MutationAssessor

Uncertain

2.6

M;.;M;.;.;M;M

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

-2.1

N;N;N;N;N;N;N

REVEL

Pathogenic

0.76

Sift

Benign

0.069

T;T;T;T;T;T;T

Sift4G

Benign

0.31

T;T;T;T;T;T;T

Polyphen

0.95

P;.;P;.;.;P;P

Vest4

0.79

MVP

1.0

MPC

2.6

ClinPred

0.99

GERP RS

3.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.51

gMVP

0.74

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over