16-79599188-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 1P and 20B. PP2BP4_StrongBP6_Very_StrongBA1

The NM_005360.5(MAF):c.715G>A(p.Ala239Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000767 in 1,058,356 control chromosomes in the GnomAD database, including 35 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0031 ( 16 hom., cov: 29)

Exomes 𝑓: 0.00040 ( 19 hom. )

Consequence

MAF
NM_005360.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.129

Publications

2 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

MAF links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

PP2

Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 22 curated pathogenic missense variants (we use a threshold of 10). The gene has 7 curated benign missense variants. Gene score misZ: 1.1779 (below the threshold of 3.09). Trascript score misZ: -0.24854 (below the threshold of 3.09). GenCC associations: The gene is linked to cerulean cataract, Fine-Lubinsky syndrome, cataract 21 multiple types, Ayme-Gripp syndrome, pulverulent cataract, cataract - microcornea syndrome.

BP4

Computational evidence support a benign effect (MetaRNN=0.0010850132).

BP6

Variant 16-79599188-C-T is Benign according to our data. Variant chr16-79599188-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 474938.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0792 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005360.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAF	NM_005360.5	MANE Select	c.715G>A	p.Ala239Thr	missense	Exon 1 of 2	NP_005351.2
	MAF	NM_001031804.3		c.715G>A	p.Ala239Thr	missense	Exon 1 of 1	NP_001026974.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
MAF	ENST00000326043.5	TSL:1 MANE Select	c.715G>A	p.Ala239Thr	missense	Exon 1 of 2	ENSP00000327048.4
MAF	ENST00000569649.1	TSL:5	c.715G>A	p.Ala239Thr	missense	Exon 1 of 2	ENSP00000455097.1
MAF	ENST00000393350.1	TSL:6	c.715G>A	p.Ala239Thr	missense	Exon 1 of 1	ENSP00000377019.1

Frequencies

GnomAD3 genomes

AF:

0.00305

AC:

445

AN:

145852

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000467

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0284

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:

0.0000152

Gnomad OTH

AF:

0.00399

GnomAD2 exomes

AF:

0.0827

AC:

AN:

532

AF XY:

0.0645

show subpopulations

Gnomad AMR exome

AF:

0.477

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.111

GnomAD4 exome

AF:

0.000402

AC:

367

AN:

912466

Hom.:

Cov.:

AF XY:

0.000366

AC XY:

156

AN XY:

426558

show subpopulations

African (AFR)

AF:

0.000112

AC:

AN:

17894

American (AMR)

AF:

0.0871

AC:

321

AN:

3686

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

8022

East Asian (EAS)

AF:

0.00

AC:

AN:

12322

South Asian (SAS)

AF:

0.00

AC:

AN:

17976

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8364

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2042

European-Non Finnish (NFE)

AF:

0.00000618

AC:

AN:

809716

Other (OTH)

AF:

0.00120

AC:

AN:

32444

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.555

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00305

AC:

445

AN:

145890

Hom.:

Cov.:

AF XY:

0.00346

AC XY:

245

AN XY:

70892

show subpopulations

African (AFR)

AF:

0.000466

AC:

AN:

40800

American (AMR)

AF:

0.0284

AC:

417

AN:

14708

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3386

East Asian (EAS)

AF:

0.00

AC:

AN:

4954

South Asian (SAS)

AF:

0.00

AC:

AN:

4782

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8250

Middle Eastern (MID)

AF:

0.00

AC:

AN:

280

European-Non Finnish (NFE)

AF:

0.0000152

AC:

AN:

65798

Other (OTH)

AF:

0.00396

AC:

AN:

2022

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

112

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00462

ExAC

AF:

0.00471

AC:

ClinVar

ClinVar submissions as Germline

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Ayme-Gripp syndrome;C1857768:Cataract 21 multiple types (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.094

BayesDel_noAF

Benign

-0.37

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.19

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.016

LIST_S2

Benign

0.41

MetaRNN

Benign

0.0011

MetaSVM

Benign

-0.78

MutationAssessor

Benign

0.0

PhyloP100

-0.13

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-0.41

REVEL

Benign

0.17

Sift

Benign

0.67

Sift4G

Benign

0.41

Polyphen

0.0

Vest4

0.13

MutPred

0.26

Gain of glycosylation at A239 (P = 0.0039)

ClinPred

0.029

GERP RS

-4.3

Varity_R

0.046

gMVP

0.20

Mutation Taster

=99/1

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over