8-143429343-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_201589.4(MAFA):c.*2C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00123 in 1,352,918 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00099 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0013 (5 hom.)
• Consequence: MAFA NM_201589.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0320

Genes affected

MAFA (HGNC:23145): (MAF bZIP transcription factor A) MAFA is a transcription factor that binds RIPE3b, a conserved enhancer element that regulates pancreatic beta cell-specific expression of the insulin gene (INS; MIM 176730) (Olbrot et al., 2002 [PubMed 12011435]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 8-143429343-G-A is Benign according to our data. Variant chr8-143429343-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3040597.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 151 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAFA	NM_201589.4	c.*2C>T		3_prime_UTR_variant	1/1	ENST00000333480.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAFA	ENST00000333480.3	c.*2C>T		3_prime_UTR_variant	1/1		NM_201589.4	P1
MAFA	ENST00000528185.1	n.389+167C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.000993 AC: 151 AN: 151988 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000524

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00193

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.00112 AC: 23 AN: 20468 Hom.: 0 AF XY: 0.00111 AC XY: 15 AN XY: 13546

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00119

Gnomad ASJ exome AF: 0.00213

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00185

Gnomad OTH exome AF: 0.00181

GnomAD4 exome AF: 0.00126 AC: 1511 AN: 1200822 Hom.: 5 Cov.: 30 AF XY: 0.00125 AC XY: 732 AN XY: 586182

Gnomad4 AFR exome AF: 0.000129

Gnomad4 AMR exome AF: 0.000539

Gnomad4 ASJ exome AF: 0.000817

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.000809

Gnomad4 NFE exome AF: 0.00140

Gnomad4 OTH exome AF: 0.00141

GnomAD4 genome AF: 0.000993 AC: 151 AN: 152096 Hom.: 1 Cov.: 32 AF XY: 0.000968 AC XY: 72 AN XY: 74374

Gnomad4 AFR AF: 0.0000722

Gnomad4 AMR AF: 0.000524

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000189

Gnomad4 NFE AF: 0.00193

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00397 Hom.: 1

Bravo AF: 0.000752

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

MAFA-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 18, 2022

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	-0.73
Cadd	Benign	16
Dann	Benign	0.96

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs752414651; hg19: chr8-144511513; COSMIC: COSV61087019;