chr16-79598581-G-GGTGTGTGTGTGT

Variant names:

• chr16-79598581-G-GGTGTGTGTGTGT
• rs5818250
• NM_005360.5:c.1118+192_1118+203dupACACACACACAC

Variant summary

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

The NM_001031804.3(MAF):​c.*188_*199dupACACACACACAC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00015 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000042 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MAF NM_001031804.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.149
• 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), G2P, Ambry Genetics
• 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001031804.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAF	NM_005360.5	MANE Select	c.1118+192_1118+203dupACACACACACAC		intron	N/A	NP_005351.2
	MAF	NM_001031804.3		c.*188_*199dupACACACACACAC		3_prime_UTR	Exon 1 of 1	NP_001026974.1	O75444-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAF	ENST00000326043.5	TSL:1 MANE Select	c.1118+192_1118+203dupACACACACACAC		intron	N/A	ENSP00000327048.4	O75444-1
	MAF	ENST00000393350.1	TSL:6	c.*188_*199dupACACACACACAC		3_prime_UTR	Exon 1 of 1	ENSP00000377019.1	O75444-2
	MAF	ENST00000569649.1	TSL:5	c.1118+192_1118+203dupACACACACACAC		intron	N/A	ENSP00000455097.1	H3BP11

Frequencies

GnomAD3 genomes AF: 0.000146 AC: 20 AN: 137232 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000222

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000145

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000506

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000109

Gnomad OTH AF: 0.000545

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000416 AC: 53 AN: 1273304 Hom.: 0 Cov.: 4 AF XY: 0.0000453 AC XY: 28 AN XY: 618736

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

African (AFR) AF: 0.000271 AC: 8 AN: 29532

American (AMR) AF: 0.00 AC: 0 AN: 29438

Ashkenazi Jewish (ASJ) AF: 0.0000499 AC: 1 AN: 20060

East Asian (EAS) AF: 0.00 AC: 0 AN: 33184

South Asian (SAS) AF: 0.000150 AC: 10 AN: 66692

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28622

Middle Eastern (MID) AF: 0.000555 AC: 2 AN: 3606

European-Non Finnish (NFE) AF: 0.0000268 AC: 27 AN: 1009266

Other (OTH) AF: 0.0000945 AC: 5 AN: 52904

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.000146 AC: 20 AN: 137320 Hom.: 0 Cov.: 0 AF XY: 0.000137 AC XY: 9 AN XY: 65920

African (AFR) AF: 0.000221 AC: 8 AN: 36148

American (AMR) AF: 0.000145 AC: 2 AN: 13800

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3336

East Asian (EAS) AF: 0.00 AC: 0 AN: 4518

South Asian (SAS) AF: 0.000507 AC: 2 AN: 3944

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8344

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 270

European-Non Finnish (NFE) AF: 0.000109 AC: 7 AN: 64238

Other (OTH) AF: 0.000539 AC: 1 AN: 1854

Alfa AF: 0.00 Hom.: 370

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.15

Splicing

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

Other links and lift over

dbSNP: rs5818250; hg19: chr16-79632478;