16-79599341-CGTGGTGGTG-CGTGGTGGTGGTG

Variant names:

• chr16-79599341-C-CGTG
• rs1029898670
• NM_005360.5:c.559_561dupCAC

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PM4_Supporting BS2

The NM_005360.5(MAF):​c.559_561dupCAC​(p.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 0.000144 in 987,410 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00019 (0 hom., cov: 30)
  • Exomes 𝑓: 0.00014 (0 hom.)
• Consequence: MAF NM_005360.5 conservative_inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.08

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 Likely_benign. Variant got -3 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_005360.5. Strenght limited to Supporting due to length of the change: 1aa.
• BS2: High AC in GnomAd4 at 28 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAF	NM_005360.5	c.559_561dupCAC	p.His187dup	conservative_inframe_insertion	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.559_561dupCAC	p.His187dup	conservative_inframe_insertion	Exon 1 of 2	1	NM_005360.5	ENSP00000327048.4
MAF	ENST00000569649.1	c.559_561dupCAC	p.His187dup	conservative_inframe_insertion	Exon 1 of 2	5		ENSP00000455097.1
MAF	ENST00000393350.1	c.559_561dupCAC	p.His187dup	conservative_inframe_insertion	Exon 1 of 1	6		ENSP00000377019.1

Frequencies

GnomAD3 genomes AF: 0.000186 AC: 27 AN: 145492 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.000123

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000204

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000609

Gnomad SAS AF: 0.00189

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000107

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000135 AC: 114 AN: 841874 Hom.: 0 Cov.: 34 AF XY: 0.000136 AC XY: 53 AN XY: 390092

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000252

Gnomad4 SAS exome AF: 0.00203

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000926

Gnomad4 OTH exome AF: 0.000215

GnomAD4 genome AF: 0.000192 AC: 28 AN: 145536 Hom.: 0 Cov.: 30 AF XY: 0.000212 AC XY: 15 AN XY: 70734

Gnomad4 AFR AF: 0.000123

Gnomad4 AMR AF: 0.000204

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000611

Gnomad4 SAS AF: 0.00189

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000107

Gnomad4 OTH AF: 0.000493

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1029898670; hg19: chr16-79633238;