rs561314990

chr16-79599188-C-Gchr16-79599188-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005360.5(MAF):c.715G>C(p.Ala239Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000686 in 145,854 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict 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. A239T) has been classified as Likely benign.

• Frequency: Genomes: 𝑓 0.0000069 (0 hom., cov: 29)
• Consequence: MAF NM_005360.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.129

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13595346).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAF	NM_005360.5	c.715G>C	p.Ala239Pro	missense_variant	1/2	ENST00000326043.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAF	ENST00000326043.5	c.715G>C	p.Ala239Pro	missense_variant	1/2	1	NM_005360.5	A2
MAF	ENST00000569649.1	c.715G>C	p.Ala239Pro	missense_variant	1/2	5		P4
MAF	ENST00000393350.1	c.715G>C	p.Ala239Pro	missense_variant	1/1			A2

Frequencies

GnomAD3 genomes AF: 0.00000686 AC: 1 AN: 145854 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.0000246

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 25

GnomAD4 genome AF: 0.00000686 AC: 1 AN: 145854 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 70840

Gnomad4 AFR AF: 0.0000246

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.086	T
BayesDel_noAF	Benign	-0.36
Cadd	Benign	15
Dann	Benign	0.84
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.069	N
LIST_S2	Benign	0.43	T;T;T
M_CAP	Pathogenic	0.46	D
MetaRNN	Benign	0.14	T;T;T
MetaSVM	Benign	-0.71	T
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-0.37	N;N;N
Sift	Benign	0.32	T;T;T
Sift4G	Benign	0.20	T;T;T
Polyphen		0.067, 0.28	.;B;B
Vest4		0.19
MutPred		0.29		Loss of helix (P = 0.0093);Loss of helix (P = 0.0093);Loss of helix (P = 0.0093);
MVP		0.75
ClinPred		0.094	T
GERP RS		-4.3
Varity_R		0.088
gMVP		0.30

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

LitVar

Other links and lift over

dbSNP: rs561314990; hg19: chr16-79633085;