16-79599201-T-G

Variant names:

• chr16-79599201-T-G
• rs779108045
• NM_005360.5:c.702A>C

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_005360.5(MAF):​c.702A>C​(p.Gly234Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0119 in 974,532 control chromosomes in the GnomAD database, including 82 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0091 (8 hom., cov: 29)
  • Exomes 𝑓: 0.012 (74 hom.)
• Consequence: MAF NM_005360.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -1.66

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]

ACMG classification

Verdict is Benign. Variant got -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 16-79599201-T-G is Benign according to our data. Variant chr16-79599201-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 259753.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.66 with no splicing effect.
• BS2: High AC in GnomAd4 at 1310 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAF	NM_005360.5	c.702A>C	p.Gly234Gly	synonymous_variant	Exon 1 of 2	ENST00000326043.5	NP_005351.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAF	ENST00000326043.5	c.702A>C	p.Gly234Gly	synonymous_variant	Exon 1 of 2	1	NM_005360.5	ENSP00000327048.4
MAF	ENST00000569649.1	c.702A>C	p.Gly234Gly	synonymous_variant	Exon 1 of 2	5		ENSP00000455097.1
MAF	ENST00000393350.1	c.702A>C	p.Gly234Gly	synonymous_variant	Exon 1 of 1	6		ENSP00000377019.1

Frequencies

GnomAD3 genomes AF: 0.00910 AC: 1310 AN: 143930 Hom.: 8 Cov.: 29

Gnomad AFR AF: 0.00188

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00323

Gnomad ASJ AF: 0.00119

Gnomad EAS AF: 0.000618

Gnomad SAS AF: 0.00232

Gnomad FIN AF: 0.0341

Gnomad MID AF: 0.00333

Gnomad NFE AF: 0.0135

Gnomad OTH AF: 0.00604

GnomAD3 exomes AF: 0.00439 AC: 1 AN: 228 Hom.: 0 AF XY: 0.00794 AC XY: 1 AN XY: 126

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00476

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0123 AC: 10254 AN: 830596 Hom.: 74 Cov.: 28 AF XY: 0.0124 AC XY: 4752 AN XY: 384606

Gnomad4 AFR exome AF: 0.00147

Gnomad4 AMR exome AF: 0.00164

Gnomad4 ASJ exome AF: 0.00114

Gnomad4 EAS exome AF: 0.000493

Gnomad4 SAS exome AF: 0.00304

Gnomad4 FIN exome AF: 0.0254

Gnomad4 NFE exome AF: 0.0131

Gnomad4 OTH exome AF: 0.00938

GnomAD4 genome AF: 0.00910 AC: 1310 AN: 143936 Hom.: 8 Cov.: 29 AF XY: 0.0102 AC XY: 715 AN XY: 69898

Gnomad4 AFR AF: 0.00188

Gnomad4 AMR AF: 0.00323

Gnomad4 ASJ AF: 0.00119

Gnomad4 EAS AF: 0.000621

Gnomad4 SAS AF: 0.00233

Gnomad4 FIN AF: 0.0341

Gnomad4 NFE AF: 0.0135

Gnomad4 OTH AF: 0.00600

Alfa AF: 0.00941 Hom.: 0

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Nov 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

MAF: BP4, BP7, BS1, BS2 -

Jan 04, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Ayme-Gripp syndrome;C1857768:Cataract 21 multiple types Benign:1

Jan 06, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Inborn genetic diseases Benign:1

Jun 07, 2024

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	4.0
DANN	Benign	0.42

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

Publications

LitVar

Other links and lift over

dbSNP: rs779108045; hg19: chr16-79633098;