rs535090775

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS1

The NM_178161.3(PTF1A):c.269G>C(p.Gly90Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000855 in 1,315,372 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0040 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00045 ( 0 hom. )

Consequence

PTF1A
NM_178161.3 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:3B:3

Conservation

PhyloP100: 0.0860

Publications

1 publications found

Variant links:

Genes affected

PTF1A (HGNC:23734): (pancreas associated transcription factor 1a) This gene encodes a protein that is a component of the pancreas transcription factor 1 complex (PTF1) and is known to have a role in mammalian pancreatic development. The protein plays a role in determining whether cells allocated to the pancreatic buds continue towards pancreatic organogenesis or revert back to duodenal fates. The protein is thought to be involved in the maintenance of exocrine pancreas-specific gene expression including elastase 1 and amylase. Mutations in this gene cause cerebellar agenesis and loss of expression is seen in ductal type pancreas cancers. [provided by RefSeq, Jul 2008]

PTF1A Gene-Disease associations (from GenCC):

pancreatic agenesis 2
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, G2P
permanent neonatal diabetes mellitus-pancreatic and cerebellar agenesis syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics, Genomics England PanelApp, Orphanet
permanent neonatal diabetes mellitus
Inheritance: AR Classification: STRONG Submitted by: Genomics England PanelApp
pancreatic agenesis
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

PTF1A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00646165).

BP6

Variant 10-23192799-G-C is Benign according to our data. Variant chr10-23192799-G-C is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 130054.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00397 (603/151914) while in subpopulation AFR AF = 0.0136 (565/41512). AF 95% confidence interval is 0.0127. There are 0 homozygotes in GnomAd4. There are 289 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178161.3. 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
	PTF1A	NM_178161.3	MANE Select	c.269G>C	p.Gly90Ala	missense	Exon 1 of 2	NP_835455.1	Q7RTS3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTF1A	ENST00000376504.4	TSL:1 MANE Select	c.269G>C	p.Gly90Ala	missense	Exon 1 of 2	ENSP00000365687.3	Q7RTS3
	PTF1A	ENST00000638469.1	TSL:5	c.114+122G>C		intron	N/A	ENSP00000491649.1	A0A1W2PQC4

Frequencies

GnomAD3 genomes

AF:

0.00397

AC:

603

AN:

151806

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0136

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00144

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00637

Gnomad NFE

AF:

0.0000589

Gnomad OTH

AF:

0.00481

GnomAD2 exomes

AF:

0.000834

AC:

AN:

11992

AF XY:

0.000540

show subpopulations

Gnomad AFR exome

AF:

0.0179

Gnomad AMR exome

AF:

0.00267

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00267

GnomAD4 exome

AF:

0.000448

AC:

521

AN:

1163458

Hom.:

Cov.:

AF XY:

0.000418

AC XY:

234

AN XY:

560076

show subpopulations

African (AFR)

AF:

0.0159

AC:

377

AN:

23680

American (AMR)

AF:

0.00105

AC:

AN:

10476

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16198

East Asian (EAS)

AF:

0.00

AC:

AN:

26850

South Asian (SAS)

AF:

0.00

AC:

AN:

38716

European-Finnish (FIN)

AF:

0.00

AC:

AN:

25940

Middle Eastern (MID)

AF:

0.00133

AC:

AN:

3754

European-Non Finnish (NFE)

AF:

0.0000732

AC:

AN:

970360

Other (OTH)

AF:

0.00120

AC:

AN:

47484

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

131

164

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00397

AC:

603

AN:

151914

Hom.:

Cov.:

AF XY:

0.00389

AC XY:

289

AN XY:

74260

show subpopulations

African (AFR)

AF:

0.0136

AC:

565

AN:

41512

American (AMR)

AF:

0.00144

AC:

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5136

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10506

Middle Eastern (MID)

AF:

0.00685

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000589

AC:

AN:

67900

Other (OTH)

AF:

0.00476

AC:

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

126

158

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00333

Hom.:

Bravo

AF:

0.00461

ExAC

AF:

0.000591

AC:

Asia WGS

AF:

0.000871

AC:

AN:

3460

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

Monogenic diabetes (1)

not provided (1)

not specified (1)

Pancreatic agenesis 2 (1)

Permanent neonatal diabetes mellitus-pancreatic and cerebellar agenesis syndrome (1)

Permanent neonatal diabetes mellitus-pancreatic and cerebellar agenesis syndrome;C4014737:Pancreatic agenesis 2 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.30

CADD

Benign

(source)

DANN

Benign

0.89

DEOGEN2

Benign

0.14

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.45

MetaRNN

Benign

0.0065

MetaSVM

Benign

-0.60

MutationAssessor

Benign

0.63

PhyloP100

0.086

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-1.1

REVEL

Benign

0.14

Sift

Benign

0.10

Sift4G

Benign

0.42

Polyphen

0.032

Vest4

0.11

MVP

0.32

ClinPred

0.0032

GERP RS

1.9

PromoterAI

0.013

Neutral

(source)

Varity_R

0.099

gMVP

0.29

Mutation Taster

=97/3

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over