16-79594427-GA-G

Variant names:

• chr16-79594427-GA-G
• rs148849596
• NM_005360.5:c.*32delT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_005360.5(MAF):​c.*32delT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0807 in 1,529,704 control chromosomes in the GnomAD database, including 5,585 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.063 (428 hom., cov: 31)
  • Exomes 𝑓: 0.083 (5157 hom.)
• Consequence: MAF NM_005360.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.852
• Publications: 3 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: Benign. The variant received -10 ACMG points.

• BP6: Variant 16-79594427-GA-G is Benign according to our data. Variant chr16-79594427-GA-G is described in ClinVar as [Benign]. Clinvar id is 1236763.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0967 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAF	NM_005360.5	c.*32delT		3_prime_UTR_variant	Exon 2 of 2	ENST00000326043.5	NP_005351.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAF	ENST00000326043.5	c.*32delT		3_prime_UTR_variant	Exon 2 of 2	1	NM_005360.5	ENSP00000327048.4
MAF	ENST00000393350.1	c.*4353delT		3_prime_UTR_variant	Exon 1 of 1	6		ENSP00000377019.1
MAF	ENST00000569649.1	c.1118+4357delT		intron_variant	Intron 1 of 1	5		ENSP00000455097.1

Frequencies

GnomAD3 genomes AF: 0.0634 AC: 9637 AN: 151942 Hom.: 428 Cov.: 31

Gnomad AFR AF: 0.0144

Gnomad AMI AF: 0.0757

Gnomad AMR AF: 0.0459

Gnomad ASJ AF: 0.144

Gnomad EAS AF: 0.00212

Gnomad SAS AF: 0.104

Gnomad FIN AF: 0.0964

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.0891

Gnomad OTH AF: 0.0690

GnomAD2 exomes AF: 0.0793 AC: 12470 AN: 157210 AF XY: 0.0843

Gnomad AFR exome AF: 0.0135

Gnomad AMR exome AF: 0.0370

Gnomad ASJ exome AF: 0.156

Gnomad EAS exome AF: 0.00185

Gnomad FIN exome AF: 0.0990

Gnomad NFE exome AF: 0.0925

Gnomad OTH exome AF: 0.0904

GnomAD4 exome AF: 0.0826 AC: 113856 AN: 1377644 Hom.: 5157 Cov.: 26 AF XY: 0.0836 AC XY: 56886 AN XY: 680774

African (AFR) AF: 0.0118 AC: 366 AN: 31138

American (AMR) AF: 0.0392 AC: 1401 AN: 35698

Ashkenazi Jewish (ASJ) AF: 0.153 AC: 3843 AN: 25084

East Asian (EAS) AF: 0.00107 AC: 38 AN: 35628

South Asian (SAS) AF: 0.109 AC: 8592 AN: 78782

European-Finnish (FIN) AF: 0.0968 AC: 4755 AN: 49108

Middle Eastern (MID) AF: 0.115 AC: 655 AN: 5674

European-Non Finnish (NFE) AF: 0.0844 AC: 89449 AN: 1059346

Other (OTH) AF: 0.0832 AC: 4757 AN: 57186

GnomAD4 genome AF: 0.0633 AC: 9630 AN: 152060 Hom.: 428 Cov.: 31 AF XY: 0.0630 AC XY: 4684 AN XY: 74296

African (AFR) AF: 0.0144 AC: 598 AN: 41510

American (AMR) AF: 0.0457 AC: 698 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.144 AC: 499 AN: 3462

East Asian (EAS) AF: 0.00213 AC: 11 AN: 5176

South Asian (SAS) AF: 0.104 AC: 502 AN: 4814

European-Finnish (FIN) AF: 0.0964 AC: 1015 AN: 10526

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.0891 AC: 6054 AN: 67974

Other (OTH) AF: 0.0687 AC: 145 AN: 2110

Alfa AF: 0.0603 Hom.: 107

Bravo AF: 0.0555

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 07, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.85
Mutation Taster		=97/3	polymorphism

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: rs148849596; hg19: chr16-79628324; COSMIC: COSV58153029;