8-143429368-C-T

Variant names:

• chr8-143429368-C-T
• rs62521874
• NM_201589.4:c.1039G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_201589.4(MAFA):​c.1039G>A​(p.Gly347Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000802 in 1,247,650 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G347C) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 8.0e-7 (0 hom.)
• Consequence: MAFA NM_201589.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.647
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14160872).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_201589.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAFA	NM_201589.4	MANE Select	c.1039G>A	p.Gly347Ser	missense	Exon 1 of 1	NP_963883.2	Q8NHW3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAFA	ENST00000333480.3	TSL:6 MANE Select	c.1039G>A	p.Gly347Ser	missense	Exon 1 of 1	ENSP00000328364.2	Q8NHW3
	MAFA	ENST00000528185.1	TSL:3	n.389+142G>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.02e-7 AC: 1 AN: 1247650 Hom.: 0 Cov.: 30 AF XY: 0.00000163 AC XY: 1 AN XY: 613658

African (AFR) AF: 0.00 AC: 0 AN: 23660

American (AMR) AF: 0.00 AC: 0 AN: 10488

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19196

East Asian (EAS) AF: 0.00 AC: 0 AN: 27190

South Asian (SAS) AF: 0.00 AC: 0 AN: 59850

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32516

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3788

European-Non Finnish (NFE) AF: 9.80e-7 AC: 1 AN: 1019896

Other (OTH) AF: 0.00 AC: 0 AN: 51066

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Uncertain	0.016	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.49	T
M_CAP	Pathogenic	0.98	D
MetaRNN	Benign	0.14	T
MetaSVM	Uncertain	-0.059	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.65
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-0.17	N
REVEL	Uncertain	0.41
Sift	Benign	0.43	T
Sift4G	Benign	1.0	T
Polyphen		0.21	B
Vest4		0.14
MutPred		0.053		Gain of glycosylation at G347 (P = 0.024)
MVP		0.33
ClinPred		0.14	T
GERP RS		3.0
Varity_R		0.19
gMVP		0.31
Mutation Taster		=93/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs62521874; hg19: chr8-144511538;