Variant 8-143429786-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_201589.4(MAFA):c.621C>G(p.His207Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0029 ( 0 hom., cov: 0)

Exomes 𝑓: 0.00090 ( 0 hom. )

Consequence

MAFA
NM_201589.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.00

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0011899769).

BS2

High AC in GnomAd4 at 14 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAFA	NM_201589.4 linkuse as main transcript	c.621C>G	p.His207Gln	missense_variant	1/1	ENST00000333480.3	NP_963883.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAFA	ENST00000333480.3 linkuse as main transcript	c.621C>G	p.His207Gln	missense_variant	1/1		NM_201589.4	ENSP00000328364	P1
MAFA	ENST00000528185.1 linkuse as main transcript	n.113C>G		non_coding_transcript_exon_variant	1/2	3

Frequencies

GnomAD3 genomes

AF:

0.00290

AC:

AN:

4822

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00505

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00256

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00757

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000519

AC:

AN:

96374

Hom.:

AF XY:

0.0000557

AC XY:

AN XY:

53818

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000515

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000113

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000902

AC:

AN:

101942

Hom.:

Cov.:

AF XY:

0.000913

AC XY:

AN XY:

48206

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00781

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000937

Gnomad4 OTH exome

AF:

0.000885

GnomAD4 genome

AF:

0.00291

AC:

AN:

4814

Hom.:

Cov.:

AF XY:

0.00203

AC XY:

AN XY:

2460

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00508

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00256

Gnomad4 NFE

AF:

0.00760

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0604

AC:

3018

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 16, 2024

The c.621C>G (p.H207Q) alteration is located in exon 1 (coding exon 1) of the MAFA gene. This alteration results from a C to G substitution at nucleotide position 621, causing the histidine (H) at amino acid position 207 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.015

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Benign

0.62

DEOGEN2

Benign

0.22

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.47

LIST_S2

Benign

0.26

MetaRNN

Benign

0.0012

MetaSVM

Uncertain

0.083

MutationAssessor

Benign

0.34

MutationTaster

Benign

0.98

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-0.37

REVEL

Benign

0.29

Sift

Benign

0.45

Sift4G

Benign

0.32

Polyphen

0.012

Vest4

0.023

MutPred

0.22

Gain of helix (P = 0.2684);

ClinPred

0.013

Varity_R

0.18

gMVP

0.21

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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