Variant 16-79594534-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_005360.5(MAF):c.1138T>A(p.Leu380Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000425 in 1,411,756 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000043 ( 0 hom. )

Consequence

MAF
NM_005360.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.394

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 links:

MAF (HGNC:):

MAF links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.35689655).

BS2

High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAF	NM_005360.5 linkuse as main transcript	c.1138T>A	p.Leu380Met	missense_variant	2/2	ENST00000326043.5	NP_005351.2	O75444-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MAF	ENST00000326043.5 linkuse as main transcript	c.1138T>A	p.Leu380Met	missense_variant	2/2	1	NM_005360.5	ENSP00000327048.4	O75444-1
MAF	ENST00000393350 linkuse as main transcript	c.*4247T>A		3_prime_UTR_variant	1/1			ENSP00000377019.1	O75444-2
MAF	ENST00000569649.1 linkuse as main transcript	c.1118+4251T>A		intron_variant		5		ENSP00000455097.1	H3BP11

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000563

AC:

AN:

177646

Hom.:

AF XY:

0.00

AC XY:

AN XY:

93956

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000140

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000425

AC:

AN:

1411756

Hom.:

Cov.:

AF XY:

0.00000430

AC XY:

AN XY:

697204

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:

0.00

Gnomad4 NFE exome

AF:

0.00000554

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 05, 2023

The c.1138T>A (p.L380M) alteration is located in exon 2 (coding exon 2) of the MAF gene. This alteration results from a T to A substitution at nucleotide position 1138, causing the leucine (L) at amino acid position 380 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Uncertain

0.16

BayesDel_noAF

Uncertain

-0.010

CADD

Benign

DANN

Uncertain

0.99

Eigen

Benign

0.036

Eigen_PC

Benign

0.00073

FATHMM_MKL

Benign

0.56

LIST_S2

Benign

0.38

M_CAP

Pathogenic

0.98

MetaRNN

Benign

0.36

MetaSVM

Uncertain

0.48

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.13

REVEL

Uncertain

0.35

Sift

Pathogenic

0.0

Sift4G

Benign

0.21

Polyphen

0.91

Vest4

0.23

MutPred

0.16

Loss of catalytic residue at L380 (P = 0.0549);

MVP

0.99

ClinPred

0.94

GERP RS

-0.64

gMVP

0.080

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over