Variant 8-143429343-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

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 (no stars).

Frequency

Genomes: 𝑓 0.00099 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 5 hom. )

Consequence

MAFA
NM_201589.4 3_prime_UTR

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.0320

Variant links:

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]

MAFA links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 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 no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAd4 at 151 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAFA	NM_201589.4 link	c.*2C>T		3_prime_UTR_variant	1/1	ENST00000333480.3	NP_963883.2	Q8NHW3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAFA	ENST00000333480 link	c.*2C>T		3_prime_UTR_variant	1/1		NM_201589.4	ENSP00000328364.2		Q8NHW3
MAFA	ENST00000528185.1 link	n.389+167C>T		intron_variant		3

Frequencies

GnomAD3 genomes

AF:

0.000993

AC:

151

AN:

151988

Hom.:

Cov.:

show subpopulations

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:

AN:

20468

Hom.:

AF XY:

0.00111

AC XY:

AN XY:

13546

show subpopulations

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.:

Cov.:

AF XY:

0.00125

AC XY:

732

AN XY:

586182

show subpopulations

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.:

Cov.:

AF XY:

0.000968

AC XY:

AN XY:

74374

show subpopulations

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.:

Bravo

AF:

0.000752

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

MAFA-related disorder

Benign:1

Likely benign, no assertion criteria provided

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

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over