rs867401075

chr16-79599292-C-Achr16-79599292-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_005360.5(MAF):c.611G>T(p.Gly204Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00224 in 979,642 control chromosomes in the GnomAD database, including 35 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G204S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.011 (28 hom., cov: 30)
  • Exomes 𝑓: 0.00077 (7 hom.)
• Consequence: MAF NM_005360.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.223

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=0.0066075623).
• BP6: Variant 16-79599292-C-A is Benign according to our data. Variant chr16-79599292-C-A is described in ClinVar as [Benign]. Clinvar id is 474936.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0107 (1550/145386) while in subpopulation AFR AF= 0.0354 (1442/40698). AF 95% confidence interval is 0.0339. There are 28 homozygotes in gnomad4. There are 716 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAd at 1548 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAF	NM_005360.5	c.611G>T	p.Gly204Val	missense_variant	1/2	ENST00000326043.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAF	ENST00000326043.5	c.611G>T	p.Gly204Val	missense_variant	1/2	1	NM_005360.5	A2
MAF	ENST00000569649.1	c.611G>T	p.Gly204Val	missense_variant	1/2	5		P4
MAF	ENST00000393350.1	c.611G>T	p.Gly204Val	missense_variant	1/1			A2

Frequencies

GnomAD3 genomes AF: 0.0106 AC: 1548 AN: 145380 Hom.: 28 Cov.: 30

Gnomad AFR AF: 0.0354

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00483

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: 0.000229

Gnomad OTH AF: 0.0109

GnomAD4 exome AF: 0.000771 AC: 643 AN: 834256 Hom.: 7 Cov.: 34 AF XY: 0.000737 AC XY: 284 AN XY: 385358

Gnomad4 AFR exome AF: 0.0323

Gnomad4 AMR exome AF: 0.00294

Gnomad4 ASJ exome AF: 0.000967

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000590

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000110

Gnomad4 OTH exome AF: 0.00139

GnomAD4 genome AF: 0.0107 AC: 1550 AN: 145386 Hom.: 28 Cov.: 30 AF XY: 0.0101 AC XY: 716 AN XY: 70638

Gnomad4 AFR AF: 0.0354

Gnomad4 AMR AF: 0.00483

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000229

Gnomad4 OTH AF: 0.0109

Alfa AF: 0.00202 Hom.: 0

ClinVar

Significance: Benign

Submissions summary: Benign:3

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 16, 2024

- -

Inborn genetic diseases Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

May 29, 2022

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 10, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.24
Cadd	Benign	20
Dann	Benign	0.95
Eigen	Benign	-0.95
Eigen_PC	Benign	-0.98
FATHMM_MKL	Benign	0.072	N
LIST_S2	Benign	0.57	T;T;T
M_CAP	Pathogenic	0.63	D
MetaRNN	Benign	0.0066	T;T;T
MetaSVM	Uncertain	-0.10	T
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	0.090	N;N;N
Sift	Uncertain	0.023	D;D;D
Sift4G	Benign	0.41	T;T;T
Polyphen		0.10, 0.015	.;B;B
Vest4		0.20
MutPred		0.17		Gain of helix (P = 0.0425);Gain of helix (P = 0.0425);Gain of helix (P = 0.0425);
MVP		0.72
ClinPred		0.071	T
GERP RS		0.96
Varity_R		0.16
gMVP		0.46

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: rs867401075; hg19: chr16-79633189;