16-79599188-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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. 14/19 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
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.129

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• 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 [Likely_benign]. Clinvar id is 474938.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-79599188-C-T is described in Lovd as [Benign].
• BA1: GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0792 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAF	NM_005360.5	c.715G>A	p.Ala239Thr	missense_variant	1/2	ENST00000326043.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAF	ENST00000326043.5	c.715G>A	p.Ala239Thr	missense_variant	1/2	1	NM_005360.5	A2
MAF	ENST00000569649.1	c.715G>A	p.Ala239Thr	missense_variant	1/2	5		P4
MAF	ENST00000393350.1	c.715G>A	p.Ala239Thr	missense_variant	1/1			A2

Frequencies

GnomAD3 genomes AF: 0.00305 AC: 445 AN: 145852 Hom.: 16 Cov.: 29

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

GnomAD3 exomes AF: 0.0827 AC: 44 AN: 532 Hom.: 7 AF XY: 0.0645 AC XY: 20 AN XY: 310

Gnomad AMR exome AF: 0.477

Gnomad SAS exome AF: 0.00

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.: 19 Cov.: 25 AF XY: 0.000366 AC XY: 156 AN XY: 426558

Gnomad4 AFR exome AF: 0.000112

Gnomad4 AMR exome AF: 0.0871

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: 0.00000618

Gnomad4 OTH exome AF: 0.00120

GnomAD4 genome AF: 0.00305 AC: 445 AN: 145890 Hom.: 16 Cov.: 29 AF XY: 0.00346 AC XY: 245 AN XY: 70892

Gnomad4 AFR AF: 0.000466

Gnomad4 AMR AF: 0.0284

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000152

Gnomad4 OTH AF: 0.00396

Bravo AF: 0.00462

ExAC AF: 0.00471 AC: 19

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

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

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 08, 2024

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 30, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.094	T
BayesDel_noAF	Benign	-0.37
Cadd	Benign	16
Dann	Benign	0.95
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.016	N
LIST_S2	Benign	0.41	T;T;T
MetaRNN	Benign	0.0011	T;T;T
MetaSVM	Benign	-0.78	T
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-0.41	N;N;N
Sift	Benign	0.67	T;T;T
Sift4G	Benign	0.41	T;T;T
Polyphen		0.0, 0.0060	.;B;B
Vest4		0.13
MutPred		0.26		Gain of glycosylation at A239 (P = 0.0039);Gain of glycosylation at A239 (P = 0.0039);Gain of glycosylation at A239 (P = 0.0039);
ClinPred		0.029	T
GERP RS		-4.3
Varity_R		0.046
gMVP		0.20

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

Other links and lift over

dbSNP: rs561314990; hg19: chr16-79633085;