rs1239219565

Variant names:

• chr16-79594534-A-C
• rs1239219565
• NM_005360.5:c.1138T>G

Your query was ambiguous. Multiple possible variants found:

• chr16-79594534-A-C
• chr16-79594534-A-G
• chr16-79594534-A-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 1P and 1B. PP2 BP4

The NM_005360.5(MAF):​c.1138T>G​(p.Leu380Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000921 in 1,411,756 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L380M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000092 (0 hom.)
• Consequence: MAF NM_005360.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.394
• Publications: 0 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: Uncertain_significance. The variant received 0 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=0.266253).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAF	NM_005360.5	c.1138T>G	p.Leu380Val	missense_variant	Exon 2 of 2	ENST00000326043.5	NP_005351.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAF	ENST00000326043.5	c.1138T>G	p.Leu380Val	missense_variant	Exon 2 of 2	1	NM_005360.5	ENSP00000327048.4
MAF	ENST00000393350.1	c.*4247T>G		3_prime_UTR_variant	Exon 1 of 1	6		ENSP00000377019.1
MAF	ENST00000569649.1	c.1118+4251T>G		intron_variant	Intron 1 of 1	5		ENSP00000455097.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000921 AC: 13 AN: 1411756 Hom.: 0 Cov.: 31 AF XY: 0.0000129 AC XY: 9 AN XY: 697204

African (AFR) AF: 0.00 AC: 0 AN: 32354

American (AMR) AF: 0.00 AC: 0 AN: 38278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25472

East Asian (EAS) AF: 0.00 AC: 0 AN: 37446

South Asian (SAS) AF: 0.00 AC: 0 AN: 80274

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50132

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5712

European-Non Finnish (NFE) AF: 0.0000120 AC: 13 AN: 1083656

Other (OTH) AF: 0.00 AC: 0 AN: 58432

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Benign	16
DANN	Benign	0.96
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.16
FATHMM_MKL	Benign	0.59	D
LIST_S2	Benign	0.48	T
M_CAP	Pathogenic	0.96	D
MetaRNN	Benign	0.27	T
MetaSVM	Uncertain	0.15	D
PhyloP100		0.39
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.12	N
REVEL	Uncertain	0.35
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.33	T
Polyphen		0.59	P
Vest4		0.17
MutPred		0.13		Loss of catalytic residue at L380 (P = 0.0825);
MVP		0.99
ClinPred		0.92	D
GERP RS		-0.64
gMVP		0.074
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs1239219565; hg19: chr16-79628431; COSMIC: COSV58154242;