16-79594639-ATTTTT-ATTTTTT

Variant names:

• chr16-79594639-A-AT
• rs66467731
• NM_005360.5:c.1119-87dupA

Variant summary

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

The NM_005360.5(MAF):​c.1119-87dupA variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0024 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0029 (0 hom.)
• Consequence: MAF NM_005360.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.184
• Publications: 7 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: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAF	NM_005360.5	c.1119-87dupA		intron_variant	Intron 1 of 1	ENST00000326043.5	NP_005351.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAF	ENST00000326043.5	c.1119-87dupA		intron_variant	Intron 1 of 1	1	NM_005360.5	ENSP00000327048.4
MAF	ENST00000393350.1	c.*4141dupA		3_prime_UTR_variant	Exon 1 of 1	6		ENSP00000377019.1
MAF	ENST00000569649.1	c.1118+4145dupA		intron_variant	Intron 1 of 1	5		ENSP00000455097.1

Frequencies

GnomAD3 genomes AF: 0.00233 AC: 343 AN: 147048 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00562

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00149

Gnomad ASJ AF: 0.000290

Gnomad EAS AF: 0.0125

Gnomad SAS AF: 0.00193

Gnomad FIN AF: 0.000225

Gnomad MID AF: 0.00641

Gnomad NFE AF: 0.000150

Gnomad OTH AF: 0.00445

GnomAD4 exome AF: 0.00291 AC: 3345 AN: 1150180 Hom.: 0 Cov.: 0 AF XY: 0.00297 AC XY: 1679 AN XY: 566052

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0112 AC: 295 AN: 26230

American (AMR) AF: 0.00462 AC: 127 AN: 27488

Ashkenazi Jewish (ASJ) AF: 0.00179 AC: 36 AN: 20086

East Asian (EAS) AF: 0.0157 AC: 477 AN: 30308

South Asian (SAS) AF: 0.00456 AC: 280 AN: 61446

European-Finnish (FIN) AF: 0.00301 AC: 106 AN: 35198

Middle Eastern (MID) AF: 0.00284 AC: 13 AN: 4574

European-Non Finnish (NFE) AF: 0.00199 AC: 1782 AN: 897492

Other (OTH) AF: 0.00484 AC: 229 AN: 47358

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00238 AC: 350 AN: 147108 Hom.: 0 Cov.: 0 AF XY: 0.00244 AC XY: 174 AN XY: 71420

African (AFR) AF: 0.00575 AC: 231 AN: 40172

American (AMR) AF: 0.00148 AC: 22 AN: 14830

Ashkenazi Jewish (ASJ) AF: 0.000290 AC: 1 AN: 3444

East Asian (EAS) AF: 0.0125 AC: 63 AN: 5020

South Asian (SAS) AF: 0.00194 AC: 9 AN: 4646

European-Finnish (FIN) AF: 0.000225 AC: 2 AN: 8890

Middle Eastern (MID) AF: 0.0104 AC: 3 AN: 288

European-Non Finnish (NFE) AF: 0.000150 AC: 10 AN: 66868

Other (OTH) AF: 0.00441 AC: 9 AN: 2040

Alfa AF: 0.00 Hom.: 1119

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.18

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: rs66467731; hg19: chr16-79628536;