16-79599292-C-T

Variant names:

• chr16-79599292-C-T
• rs867401075
• NM_005360.5:c.611G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 3P and 2B. PM2 PP2 BP4_Moderate

The NM_005360.5(MAF):​c.611G>A​(p.Gly204Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000012 in 834,256 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G204V) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000012 (0 hom.)
• Consequence: MAF NM_005360.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.223
• Publications: 1 publications found

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

ENSG00000278058 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• 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=0.13264936).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAF	NM_005360.5	c.611G>A	p.Gly204Asp	missense_variant	Exon 1 of 2	ENST00000326043.5	NP_005351.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAF	ENST00000326043.5	c.611G>A	p.Gly204Asp	missense_variant	Exon 1 of 2	1	NM_005360.5	ENSP00000327048.4

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000120 AC: 1 AN: 834256 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 385358

African (AFR) AF: 0.00 AC: 0 AN: 15786

American (AMR) AF: 0.00 AC: 0 AN: 1020

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5170

East Asian (EAS) AF: 0.00 AC: 0 AN: 3640

South Asian (SAS) AF: 0.00 AC: 0 AN: 16946

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 340

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1620

European-Non Finnish (NFE) AF: 0.00000131 AC: 1 AN: 762380

Other (OTH) AF: 0.00 AC: 0 AN: 27354

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Uncertain	0.013	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	18
DANN	Benign	0.39
DEOGEN2	Benign	0.17	.;.;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.062	N
LIST_S2	Benign	0.53	T;T;T
M_CAP	Pathogenic	0.67	D
MetaRNN	Benign	0.13	T;T;T
MetaSVM	Benign	-0.41	T
MutationAssessor	Benign	0.34	.;N;N
PhyloP100		-0.22
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	0.42	N;N;N
REVEL	Benign	0.25
Sift	Benign	0.47	T;T;T
Sift4G	Benign	0.72	T;T;T
Polyphen		0.19, 0.069	.;B;B
Vest4		0.15
MutPred		0.13		Gain of loop (P = 0.0851);Gain of loop (P = 0.0851);Gain of loop (P = 0.0851);
MVP		0.71
ClinPred		0.045	T
GERP RS		0.96
Varity_R		0.12
gMVP		0.48
Mutation Taster		=93/7	polymorphism

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

Other links and lift over

dbSNP: rs867401075; hg19: chr16-79633189;