rs140303158

Positions:

• chr16-79599021-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_005360.5(MAF):​c.882G>A​(p.Arg294=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000884 in 1,613,618 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00061 (0 hom., cov: 30)
  • Exomes 𝑓: 0.00091 (3 hom.)
• Consequence: MAF NM_005360.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 3.14

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 Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP6: Variant 16-79599021-C-T is Benign according to our data. Variant chr16-79599021-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 259754.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=3.14 with no splicing effect.
• BS2: High AC in GnomAd4 at 92 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAF	NM_005360.5	c.882G>A	p.Arg294=	synonymous_variant	1/2	ENST00000326043.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAF	ENST00000326043.5	c.882G>A	p.Arg294=	synonymous_variant	1/2	1	NM_005360.5	A2
MAF	ENST00000569649.1	c.882G>A	p.Arg294=	synonymous_variant	1/2	5		P4
MAF	ENST00000393350.1	c.882G>A	p.Arg294=	synonymous_variant	1/1			A2

Frequencies

GnomAD3 genomes AF: 0.000606 AC: 92 AN: 151902 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000190

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00119

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000658 AC: 164 AN: 249136 Hom.: 1 AF XY: 0.000615 AC XY: 83 AN XY: 135046

Gnomad AFR exome AF: 0.000188

Gnomad AMR exome AF: 0.000928

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000186

Gnomad NFE exome AF: 0.00108

Gnomad OTH exome AF: 0.000657

GnomAD4 exome AF: 0.000913 AC: 1334 AN: 1461600 Hom.: 3 Cov.: 36 AF XY: 0.000901 AC XY: 655 AN XY: 727084

Gnomad4 AFR exome AF: 0.000149

Gnomad4 AMR exome AF: 0.000850

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.000245

Gnomad4 NFE exome AF: 0.00111

Gnomad4 OTH exome AF: 0.000778

GnomAD4 genome AF: 0.000605 AC: 92 AN: 152018 Hom.: 0 Cov.: 30 AF XY: 0.000484 AC XY: 36 AN XY: 74314

Gnomad4 AFR AF: 0.000120

Gnomad4 AMR AF: 0.000262

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000190

Gnomad4 NFE AF: 0.00119

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00101 Hom.: 0

Bravo AF: 0.000729

EpiCase AF: 0.00115

EpiControl AF: 0.000949

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Ayme-Gripp syndrome;C1857768:Cataract 21 multiple types Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Nov 27, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	16
DANN	Benign	0.97

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: rs140303158; hg19: chr16-79632918;