rs727502813

Positions:

• chr16-79599731-T-G
• chr16-79599731-T-C
• chr16-79599731-T-A

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1 PM2 PM5

The NM_005360.5(MAF):​c.172A>C​(p.Thr58Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. T58A) has been classified as Pathogenic.

• Frequency: Genomes: not found (cov: 30)
• Consequence: MAF NM_005360.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.13

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 (HGNC:):

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM1: In a region_of_interest Disordered (size 27) in uniprot entity MAF_HUMAN there are 6 pathogenic changes around while only 0 benign (100%) in NM_005360.5
• PM2: Very rare variant in population databases, with high coverage
• PM5: Other missense variant is known to change same aminoacid residue: Variant chr16-79599731-T-C is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAF	NM_005360.5	c.172A>C	p.Thr58Pro	missense_variant	1/2	ENST00000326043.5	NP_005351.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAF	ENST00000326043.5	c.172A>C	p.Thr58Pro	missense_variant	1/2	1	NM_005360.5	ENSP00000327048.4
MAF	ENST00000569649.1	c.172A>C	p.Thr58Pro	missense_variant	1/2	5		ENSP00000455097.1
MAF	ENST00000393350.1	c.172A>C	p.Thr58Pro	missense_variant	1/1	6		ENSP00000377019.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.79
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Pathogenic	30
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.78	.;.;D
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.77	T;T;T
M_CAP	Pathogenic	0.97	D
MetaRNN	Uncertain	0.54	D;D;D
MetaSVM	Pathogenic	1.0	D
MutationAssessor	Uncertain	2.2	.;M;M
PrimateAI	Pathogenic	0.95	D
PROVEAN	Uncertain	-3.3	D;D;D
REVEL	Pathogenic	0.69
Sift	Uncertain	0.0060	D;D;D
Sift4G	Uncertain	0.0040	D;D;D
Polyphen		1.0, 0.99	.;D;D
Vest4		0.41
MutPred		0.15		Loss of phosphorylation at T58 (P = 0.008);Loss of phosphorylation at T58 (P = 0.008);Loss of phosphorylation at T58 (P = 0.008);
MVP		0.99
ClinPred		0.95	D
GERP RS		2.9
Varity_R		0.73
gMVP		0.82

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-79633628; COSMIC: COSV100391742; COSMIC: COSV100391742;