16-79598581-G-GGTGTGTGT

Variant names:

• chr16-79598581-G-GGTGTGTGT
• rs5818250
• NM_005360.5:c.1118+196_1118+203dupACACACAC

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_005360.5(MAF):​c.1118+196_1118+203dupACACACAC variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.011 (21 hom., cov: 0)
  • Exomes 𝑓: 0.012 (7 hom.)
  • Failed GnomAD Quality Control
• Consequence: MAF NM_005360.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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), 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: Likely_benign. The variant received -6 ACMG points.

• BP6: Variant 16-79598581-G-GGTGTGTGT is Benign according to our data. Variant chr16-79598581-G-GGTGTGTGT is described in ClinVar as [Likely_benign]. Clinvar id is 1344968.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 21 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAF	NM_005360.5	c.1118+196_1118+203dupACACACAC		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.1118+196_1118+203dupACACACAC		intron_variant	Intron 1 of 1	1	NM_005360.5	ENSP00000327048.4
MAF	ENST00000393350.1	c.*192_*199dupACACACAC		3_prime_UTR_variant	Exon 1 of 1	6		ENSP00000377019.1
MAF	ENST00000569649.1	c.1118+196_1118+203dupACACACAC		intron_variant	Intron 1 of 1	5		ENSP00000455097.1

Frequencies

GnomAD3 genomes AF: 0.0114 AC: 1568 AN: 137208 Hom.: 21 Cov.: 0

Gnomad AFR AF: 0.00469

Gnomad AMI AF: 0.0138

Gnomad AMR AF: 0.0107

Gnomad ASJ AF: 0.0501

Gnomad EAS AF: 0.00398

Gnomad SAS AF: 0.00557

Gnomad FIN AF: 0.00876

Gnomad MID AF: 0.0207

Gnomad NFE AF: 0.0144

Gnomad OTH AF: 0.0142

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0121 AC: 15379 AN: 1269764 Hom.: 7 Cov.: 4 AF XY: 0.0118 AC XY: 7263 AN XY: 617096

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

African (AFR) AF: 0.00339 AC: 100 AN: 29496

American (AMR) AF: 0.00894 AC: 263 AN: 29408

Ashkenazi Jewish (ASJ) AF: 0.0531 AC: 1057 AN: 19894

East Asian (EAS) AF: 0.00341 AC: 113 AN: 33158

South Asian (SAS) AF: 0.00650 AC: 433 AN: 66616

European-Finnish (FIN) AF: 0.0106 AC: 303 AN: 28604

Middle Eastern (MID) AF: 0.0109 AC: 39 AN: 3594

European-Non Finnish (NFE) AF: 0.0123 AC: 12359 AN: 1006222

Other (OTH) AF: 0.0135 AC: 712 AN: 52772

⚠️ 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: 0.0114 AC: 1565 AN: 137296 Hom.: 21 Cov.: 0 AF XY: 0.0111 AC XY: 732 AN XY: 65910

African (AFR) AF: 0.00468 AC: 169 AN: 36144

American (AMR) AF: 0.0107 AC: 147 AN: 13796

Ashkenazi Jewish (ASJ) AF: 0.0501 AC: 167 AN: 3336

East Asian (EAS) AF: 0.00376 AC: 17 AN: 4516

South Asian (SAS) AF: 0.00532 AC: 21 AN: 3944

European-Finnish (FIN) AF: 0.00876 AC: 73 AN: 8338

Middle Eastern (MID) AF: 0.0222 AC: 6 AN: 270

European-Non Finnish (NFE) AF: 0.0144 AC: 927 AN: 64230

Other (OTH) AF: 0.0140 AC: 26 AN: 1854

Alfa AF: 0.00531 Hom.: 370

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 14, 2020

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.15
Mutation Taster		=100/0	polymorphism

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;