16-79599908-TGCCGCCGCCGCCGCC-TGCCGCCGCCGCC

Variant names:

• chr16-79599908-TGCC-T
• rs5818251
• NM_005360.5:c.-9_-7delGGC

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_005360.5(MAF):​c.-9_-7delGGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.715 in 1,551,450 control chromosomes in the GnomAD database, including 384,130 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.77 (44286 hom., cov: 0)
  • Exomes 𝑓: 0.71 (339844 hom.)
• Consequence: MAF NM_005360.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.735
• 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

ENSG00000278058 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 16-79599908-TGCC-T is Benign according to our data. Variant chr16-79599908-TGCC-T is described in ClinVar as Benign. ClinVar VariationId is 259752.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.903 is higher than 0.05.

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.-9_-7delGGC		5_prime_UTR	Exon 1 of 2	NP_005351.2
	MAF	NM_001031804.3		c.-9_-7delGGC		5_prime_UTR	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.-9_-7delGGC		5_prime_UTR	Exon 1 of 2	ENSP00000327048.4
	ENSG00000278058	ENST00000767269.1		n.47_49delCGC		non_coding_transcript_exon	Exon 1 of 3
	MAF	ENST00000393350.1	TSL:6	c.-9_-7delGGC		5_prime_UTR	Exon 1 of 1	ENSP00000377019.1

Frequencies

GnomAD3 genomes AF: 0.765 AC: 115229 AN: 150592 Hom.: 44264 Cov.: 0

Gnomad AFR AF: 0.794

Gnomad AMI AF: 0.723

Gnomad AMR AF: 0.770

Gnomad ASJ AF: 0.712

Gnomad EAS AF: 0.926

Gnomad SAS AF: 0.657

Gnomad FIN AF: 0.820

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.737

Gnomad OTH AF: 0.765

GnomAD2 exomes AF: 0.727 AC: 142149 AN: 195638 AF XY: 0.720

Gnomad AFR exome AF: 0.754

Gnomad AMR exome AF: 0.783

Gnomad ASJ exome AF: 0.700

Gnomad EAS exome AF: 0.906

Gnomad FIN exome AF: 0.776

Gnomad NFE exome AF: 0.701

Gnomad OTH exome AF: 0.717

GnomAD4 exome AF: 0.709 AC: 993339 AN: 1400756 Hom.: 339844 AF XY: 0.706 AC XY: 492771 AN XY: 697712

African (AFR) AF: 0.752 AC: 24266 AN: 32264

American (AMR) AF: 0.755 AC: 32506 AN: 43048

Ashkenazi Jewish (ASJ) AF: 0.684 AC: 17311 AN: 25312

East Asian (EAS) AF: 0.878 AC: 32920 AN: 37514

South Asian (SAS) AF: 0.635 AC: 53311 AN: 83992

European-Finnish (FIN) AF: 0.744 AC: 27352 AN: 36768

Middle Eastern (MID) AF: 0.683 AC: 3084 AN: 4516

European-Non Finnish (NFE) AF: 0.705 AC: 761283 AN: 1079244

Other (OTH) AF: 0.711 AC: 41306 AN: 58098

GnomAD4 genome AF: 0.765 AC: 115300 AN: 150694 Hom.: 44286 Cov.: 0 AF XY: 0.768 AC XY: 56543 AN XY: 73608

African (AFR) AF: 0.794 AC: 32637 AN: 41118

American (AMR) AF: 0.770 AC: 11695 AN: 15182

Ashkenazi Jewish (ASJ) AF: 0.712 AC: 2461 AN: 3458

East Asian (EAS) AF: 0.925 AC: 4594 AN: 4964

South Asian (SAS) AF: 0.656 AC: 3127 AN: 4770

European-Finnish (FIN) AF: 0.820 AC: 8539 AN: 10418

Middle Eastern (MID) AF: 0.759 AC: 220 AN: 290

European-Non Finnish (NFE) AF: 0.737 AC: 49772 AN: 67504

Other (OTH) AF: 0.767 AC: 1604 AN: 2090

Alfa AF: 0.695 Hom.: 4066

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Ayme-Gripp syndrome Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Cataract 21 multiple types Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided Benign:1

Aug 15, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.73
Mutation Taster		=294/6	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs5818251; hg19: chr16-79633805; COSMIC: COSV108152492;