NM_005360.5:c.702A>C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 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: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId 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 Homozygotes in GnomAd4 at 8 AD,AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAF	NM_005360.5	MANE Select	c.702A>C	p.Gly234Gly	synonymous	Exon 1 of 2	NP_005351.2
	MAF	NM_001031804.3		c.702A>C	p.Gly234Gly	synonymous	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.702A>C	p.Gly234Gly	synonymous	Exon 1 of 2	ENSP00000327048.4	O75444-1
	MAF	ENST00000569649.1	TSL:5	c.702A>C	p.Gly234Gly	synonymous	Exon 1 of 2	ENSP00000455097.1	H3BP11
	MAF	ENST00000393350.1	TSL:6	c.702A>C	p.Gly234Gly	synonymous	Exon 1 of 1	ENSP00000377019.1	O75444-2

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

GnomAD2 exomes AF: 0.00439 AC: 1 AN: 228 AF XY: 0.00794

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

African (AFR) AF: 0.00147 AC: 23 AN: 15606

American (AMR) AF: 0.00164 AC: 2 AN: 1222

Ashkenazi Jewish (ASJ) AF: 0.00114 AC: 6 AN: 5286

East Asian (EAS) AF: 0.000493 AC: 2 AN: 4058

South Asian (SAS) AF: 0.00304 AC: 52 AN: 17114

European-Finnish (FIN) AF: 0.0254 AC: 30 AN: 1180

Middle Eastern (MID) AF: 0.00122 AC: 2 AN: 1640

European-Non Finnish (NFE) AF: 0.0131 AC: 9880 AN: 757080

Other (OTH) AF: 0.00938 AC: 257 AN: 27410

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

African (AFR) AF: 0.00188 AC: 75 AN: 39878

American (AMR) AF: 0.00323 AC: 47 AN: 14564

Ashkenazi Jewish (ASJ) AF: 0.00119 AC: 4 AN: 3368

East Asian (EAS) AF: 0.000621 AC: 3 AN: 4834

South Asian (SAS) AF: 0.00233 AC: 11 AN: 4718

European-Finnish (FIN) AF: 0.0341 AC: 276 AN: 8102

Middle Eastern (MID) AF: 0.00365 AC: 1 AN: 274

European-Non Finnish (NFE) AF: 0.0135 AC: 881 AN: 65294

Other (OTH) AF: 0.00600 AC: 12 AN: 2000

Alfa AF: 0.00941 Hom.: 0

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Ayme-Gripp syndrome;C1857768:Cataract 21 multiple types (1)
-	-	1	Inborn genetic diseases (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	4.0
DANN	Benign	0.42
PhyloP100		-1.7
Mutation Taster		=100/0	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: rs779108045; hg19: chr16-79633098; COSMIC: COSV108152500; COSMIC: COSV108152500;