8-143430216-G-A

Variant names:

• chr8-143430216-G-A
• rs1554635488
• NM_201589.4:c.191C>T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP5_Moderate

The NM_201589.4(MAFA):​c.191C>T​(p.Ser64Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★).

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MAFA NM_201589.4 missense
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:2
• Conservation: PhyloP100: 6.74
• Publications: 2 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 8-143430216-G-A is Pathogenic according to our data. Variant chr8-143430216-G-A is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 496645.Status of the report is criteria_provided_single_submitter, 1 stars.

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.191C>T	p.Ser64Phe	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.191C>T	p.Ser64Phe	missense	Exon 1 of 1	ENSP00000328364.2	Q8NHW3

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1167828 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 573570

African (AFR) AF: 0.00 AC: 0 AN: 22756

American (AMR) AF: 0.00 AC: 0 AN: 19556

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17258

East Asian (EAS) AF: 0.00 AC: 0 AN: 20346

South Asian (SAS) AF: 0.00 AC: 0 AN: 58440

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35740

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4026

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 945772

Other (OTH) AF: 0.00 AC: 0 AN: 43934

GnomAD4 genome Cov.: 29

ClinVar

ClinVar submissions

Significance: Likely pathogenic

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
2	-	-	Islet cell adenomatosis (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.030
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.71	D
Eigen	Uncertain	0.20
Eigen_PC	Benign	0.17
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.87	D
M_CAP	Pathogenic	0.96	D
MetaRNN	Uncertain	0.61	D
MetaSVM	Pathogenic	0.87	D
MutationAssessor	Uncertain	2.4	M
PhyloP100		6.7
PrimateAI	Pathogenic	0.98	D
PROVEAN	Uncertain	-3.5	D
REVEL	Uncertain	0.59
Sift	Benign	0.038	D
Sift4G	Pathogenic	0.0010	D
Varity_R		0.39
gMVP		0.55
Mutation Taster		=16/84	disease causing (ClinVar)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1554635488; hg19: chr8-144512386;