rs727502767

Positions:

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

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 6P and 1B. PM1 PM2 PM5 BP4

The NM_005360.5(MAF):​c.172A>T​(p.Thr58Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. 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 Uncertain_significance. Variant got 5 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].
• BP4: Computational evidence support a benign effect (MetaRNN=0.42325094).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAF	NM_005360.5	c.172A>T	p.Thr58Ser	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>T	p.Thr58Ser	missense_variant	1/2	1	NM_005360.5	ENSP00000327048.4
MAF	ENST00000569649.1	c.172A>T	p.Thr58Ser	missense_variant	1/2	5		ENSP00000455097.1
MAF	ENST00000393350.1	c.172A>T	p.Thr58Ser	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	0.86
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Pathogenic	27
DANN	Benign	0.95
DEOGEN2	Benign	0.35	.;.;T
Eigen	Uncertain	0.20
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.78	T;T;T
M_CAP	Pathogenic	0.92	D
MetaRNN	Benign	0.42	T;T;T
MetaSVM	Uncertain	0.75	D
MutationAssessor	Benign	1.1	.;L;L
PrimateAI	Pathogenic	0.95	D
PROVEAN	Benign	-1.8	N;N;N
REVEL	Uncertain	0.44
Sift	Benign	0.15	T;T;T
Sift4G	Benign	0.23	T;T;T
Polyphen		0.97, 0.98	.;D;D
Vest4		0.43
MutPred		0.13		Loss of stability (P = 0.1307);Loss of stability (P = 0.1307);Loss of stability (P = 0.1307);
MVP		0.98
ClinPred		0.84	D
GERP RS		2.9
Varity_R		0.30
gMVP		0.73

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;