NM_005360.5:c.1179G>A

Variant names:

• chr16-79594493-C-T
• rs149118803
• NM_005360.5:c.1179G>A

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_005360.5(MAF):​c.1179G>A​(p.Gln393Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000896 in 1,566,318 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00078 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00091 (0 hom.)
• Consequence: MAF NM_005360.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.0170

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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP6: Variant 16-79594493-C-T is Benign according to our data. Variant chr16-79594493-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1168532.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-79594493-C-T is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=0.017 with no splicing effect.
• BS2: High AC in GnomAd4 at 119 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAF	NM_005360.5	c.1179G>A	p.Gln393Gln	synonymous_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.1179G>A	p.Gln393Gln	synonymous_variant	Exon 2 of 2	1	NM_005360.5	ENSP00000327048.4
MAF	ENST00000393350	c.*4288G>A		3_prime_UTR_variant	Exon 1 of 1			ENSP00000377019.1
MAF	ENST00000569649.1	c.1118+4292G>A		intron_variant	Intron 1 of 1	5		ENSP00000455097.1

Frequencies

GnomAD3 genomes AF: 0.000782 AC: 119 AN: 152078 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000242

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00151

Gnomad OTH AF: 0.000957

GnomAD3 exomes AF: 0.000634 AC: 116 AN: 182986 Hom.: 0 AF XY: 0.000589 AC XY: 57 AN XY: 96844

Gnomad AFR exome AF: 0.0000879

Gnomad AMR exome AF: 0.000107

Gnomad ASJ exome AF: 0.000883

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000289

Gnomad FIN exome AF: 0.000353

Gnomad NFE exome AF: 0.00117

Gnomad OTH exome AF: 0.000804

GnomAD4 exome AF: 0.000909 AC: 1285 AN: 1414240 Hom.: 0 Cov.: 31 AF XY: 0.000926 AC XY: 647 AN XY: 698686

Gnomad4 AFR exome AF: 0.000370

Gnomad4 AMR exome AF: 0.000129

Gnomad4 ASJ exome AF: 0.000706

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000398

Gnomad4 FIN exome AF: 0.000219

Gnomad4 NFE exome AF: 0.00107

Gnomad4 OTH exome AF: 0.000803

GnomAD4 genome AF: 0.000782 AC: 119 AN: 152078 Hom.: 0 Cov.: 32 AF XY: 0.000539 AC XY: 40 AN XY: 74278

Gnomad4 AFR AF: 0.000242

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000189

Gnomad4 NFE AF: 0.00151

Gnomad4 OTH AF: 0.000957

Alfa AF: 0.00117 Hom.: 0

Bravo AF: 0.000699

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

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

Oct 23, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

Aug 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

MAF: BP4, BP7 -

MAF-related disorder Benign:1

May 03, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	6.4
DANN	Benign	0.71

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: rs149118803; hg19: chr16-79628390;