16-79599341-C-CGTGGTG

Variant names:

• chr16-79599341-C-CGTGGTG
• rs1029898670
• NM_005360.5:c.556_561dupCACCAC

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM4

The NM_005360.5(MAF):​c.556_561dupCACCAC​(p.His186_His187dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000405 in 987,396 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000027 (0 hom., cov: 30)
  • Exomes 𝑓: 0.000043 (0 hom.)
• Consequence: MAF NM_005360.5 conservative_inframe_insertion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.08
• Publications: 0 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 2 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_005360.5.

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.556_561dupCACCAC	p.His186_His187dup	conservative_inframe_insertion	Exon 1 of 2	NP_005351.2
	MAF	NM_001031804.3		c.556_561dupCACCAC	p.His186_His187dup	conservative_inframe_insertion	Exon 1 of 1	NP_001026974.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAF	ENST00000326043.5	TSL:1 MANE Select	c.556_561dupCACCAC	p.His186_His187dup	conservative_inframe_insertion	Exon 1 of 2	ENSP00000327048.4
	MAF	ENST00000569649.1	TSL:5	c.556_561dupCACCAC	p.His186_His187dup	conservative_inframe_insertion	Exon 1 of 2	ENSP00000455097.1
	MAF	ENST00000393350.1	TSL:6	c.556_561dupCACCAC	p.His186_His187dup	conservative_inframe_insertion	Exon 1 of 1	ENSP00000377019.1

Frequencies

GnomAD3 genomes AF: 0.0000275 AC: 4 AN: 145492 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.0000492

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000305

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000428 AC: 36 AN: 841904 Hom.: 0 Cov.: 34 AF XY: 0.0000436 AC XY: 17 AN XY: 390102

African (AFR) AF: 0.000126 AC: 2 AN: 15920

American (AMR) AF: 0.00 AC: 0 AN: 1424

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5342

East Asian (EAS) AF: 0.00 AC: 0 AN: 3968

South Asian (SAS) AF: 0.000116 AC: 2 AN: 17266

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1434

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1648

European-Non Finnish (NFE) AF: 0.0000404 AC: 31 AN: 767030

Other (OTH) AF: 0.0000359 AC: 1 AN: 27872

GnomAD4 genome AF: 0.0000275 AC: 4 AN: 145492 Hom.: 0 Cov.: 30 AF XY: 0.0000141 AC XY: 1 AN XY: 70676

African (AFR) AF: 0.0000492 AC: 2 AN: 40646

American (AMR) AF: 0.00 AC: 0 AN: 14680

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3376

East Asian (EAS) AF: 0.00 AC: 0 AN: 4928

South Asian (SAS) AF: 0.00 AC: 0 AN: 4772

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8294

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 304

European-Non Finnish (NFE) AF: 0.0000305 AC: 2 AN: 65578

Other (OTH) AF: 0.00 AC: 0 AN: 2012

Alfa AF: 0.00 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Mar 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

MAF: PM4

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.1
Mutation Taster		=23/77	disease causing

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1029898670; hg19: chr16-79633238;