chr16-79599292-C-A

Variant names:

• chr16-79599292-C-A
• rs867401075
• NM_005360.5:c.611G>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 1P and 20B. PP2 BP4_Strong BP6_Very_Strong BS1 BS2

The NM_005360.5(MAF):​c.611G>T​(p.Gly204Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00224 in 979,642 control chromosomes in the GnomAD database, including 35 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G204S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.011 (28 hom., cov: 30)
  • Exomes 𝑓: 0.00077 (7 hom.)
• Consequence: MAF NM_005360.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.223
• 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

ENSG00000278058 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• PP2: Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 22 curated pathogenic missense variants (we use a threshold of 10). The gene has 7 curated benign missense variants. Gene score misZ: 1.1779 (below the threshold of 3.09). Trascript score misZ: -0.24854 (below the threshold of 3.09). GenCC associations: The gene is linked to cerulean cataract, Fine-Lubinsky syndrome, cataract 21 multiple types, Ayme-Gripp syndrome, pulverulent cataract, cataract - microcornea syndrome.
• BP4: Computational evidence support a benign effect (MetaRNN=0.0066075623).
• BP6: Variant 16-79599292-C-A is Benign according to our data. Variant chr16-79599292-C-A is described in ClinVar as Benign. ClinVar VariationId is 474936.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0107 (1550/145386) while in subpopulation AFR AF = 0.0354 (1442/40698). AF 95% confidence interval is 0.0339. There are 28 homozygotes in GnomAd4. There are 716 alleles in the male GnomAd4 subpopulation. Median coverage is 30. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 28 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.611G>T	p.Gly204Val	missense	Exon 1 of 2	NP_005351.2
	MAF	NM_001031804.3		c.611G>T	p.Gly204Val	missense	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.611G>T	p.Gly204Val	missense	Exon 1 of 2	ENSP00000327048.4	O75444-1
	MAF	ENST00000569649.1	TSL:5	c.611G>T	p.Gly204Val	missense	Exon 1 of 2	ENSP00000455097.1	H3BP11
	MAF	ENST00000393350.1	TSL:6	c.611G>T	p.Gly204Val	missense	Exon 1 of 1	ENSP00000377019.1	O75444-2

Frequencies

GnomAD3 genomes AF: 0.0106 AC: 1548 AN: 145380 Hom.: 28 Cov.: 30

Gnomad AFR AF: 0.0354

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00483

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000229

Gnomad OTH AF: 0.0109

GnomAD2 exomes AF: 0.00 AC: 0 AN: 8 AF XY: 0.00

Gnomad NFE exome AF: 0.00

GnomAD4 exome AF: 0.000771 AC: 643 AN: 834256 Hom.: 7 Cov.: 34 AF XY: 0.000737 AC XY: 284 AN XY: 385358

African (AFR) AF: 0.0323 AC: 510 AN: 15786

American (AMR) AF: 0.00294 AC: 3 AN: 1020

Ashkenazi Jewish (ASJ) AF: 0.000967 AC: 5 AN: 5170

East Asian (EAS) AF: 0.00 AC: 0 AN: 3640

South Asian (SAS) AF: 0.0000590 AC: 1 AN: 16946

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 340

Middle Eastern (MID) AF: 0.00123 AC: 2 AN: 1620

European-Non Finnish (NFE) AF: 0.000110 AC: 84 AN: 762380

Other (OTH) AF: 0.00139 AC: 38 AN: 27354

GnomAD4 genome AF: 0.0107 AC: 1550 AN: 145386 Hom.: 28 Cov.: 30 AF XY: 0.0101 AC XY: 716 AN XY: 70638

African (AFR) AF: 0.0354 AC: 1442 AN: 40698

American (AMR) AF: 0.00483 AC: 71 AN: 14712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3380

East Asian (EAS) AF: 0.00 AC: 0 AN: 4906

South Asian (SAS) AF: 0.00 AC: 0 AN: 4756

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8198

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 272

European-Non Finnish (NFE) AF: 0.000229 AC: 15 AN: 65534

Other (OTH) AF: 0.0109 AC: 22 AN: 2026

Alfa AF: 0.00202 Hom.: 0

ClinVar

ClinVar submissions

Significance: 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)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	20
DANN	Benign	0.95
DEOGEN2	Benign	0.17	T
Eigen	Benign	-0.95
Eigen_PC	Benign	-0.98
FATHMM_MKL	Benign	0.072	N
LIST_S2	Benign	0.57	T
M_CAP	Pathogenic	0.63	D
MetaRNN	Benign	0.0066	T
MetaSVM	Uncertain	-0.10	T
MutationAssessor	Benign	0.34	N
PhyloP100		-0.22
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	0.090	N
REVEL	Benign	0.19
Sift	Uncertain	0.023	D
Sift4G	Benign	0.41	T
Polyphen		0.10	B
Vest4		0.20
MutPred		0.17		Gain of helix (P = 0.0425)
MVP		0.72
ClinPred		0.071	T
GERP RS		0.96
Varity_R		0.16
gMVP		0.46
Mutation Taster		=99/1	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: rs867401075; hg19: chr16-79633189;