rs864309678

Variant names:

• chr16-79599084-C-G
• rs864309678
• NM_005360.5:c.819G>C

Your query was ambiguous. Multiple possible variants found:

• chr16-79599084-C-G
• chr16-79599084-C-T

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP2 PP3_Moderate PP5

The NM_005360.5(MAF):​c.819G>C​(p.Glu273Asp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E273K) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 30)
• Consequence: MAF NM_005360.5 missense
• Clinical Significance: Likely pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 5.83
• Publications: 4 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

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 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.
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.917
• PP5: Variant 16-79599084-C-G is Pathogenic according to our data. Variant chr16-79599084-C-G is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 217325.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAF	NM_005360.5	c.819G>C	p.Glu273Asp	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.819G>C	p.Glu273Asp	missense_variant	Exon 1 of 2	1	NM_005360.5	ENSP00000327048.4
MAF	ENST00000569649.1	c.819G>C	p.Glu273Asp	missense_variant	Exon 1 of 2	5		ENSP00000455097.1
MAF	ENST00000393350.1	c.819G>C	p.Glu273Asp	missense_variant	Exon 1 of 1	6		ENSP00000377019.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 30

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Developmental cataract Pathogenic:1

Jan 09, 2015

Eye Genetics Research Group, Children's Medical Research Institute

Significance: Likely pathogenic

Review Status: no assertion criteria provided

Collection Method: research

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.030
CADD	Pathogenic	33
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0	.;.;D
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Pathogenic	0.98	D;D;D
M_CAP	Pathogenic	0.47	D
MetaRNN	Pathogenic	0.92	D;D;D
MetaSVM	Uncertain	0.69	D
MutationAssessor	Benign	0.0	.;L;L
PhyloP100		5.8
PrimateAI	Pathogenic	0.95	D
PROVEAN	Uncertain	-2.6	D;D;D
REVEL	Benign	0.0
Sift	Benign	0.14	T;T;T
Sift4G	Uncertain	0.033	D;D;D
Vest4		0.95
ClinPred		0.98	D
GERP RS		2.8
Varity_R		0.44
gMVP		0.74
Mutation Taster		=4/96	disease causing (ClinVar)

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: rs864309678; hg19: chr16-79632981;