rs1162744670

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_178161.3(PTF1A):c.265C>A(p.Leu89Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000116 in 1,313,992 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

PTF1A
NM_178161.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:4

Conservation

PhyloP100: 0.0790

Publications

0 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: G2P, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
permanent neonatal diabetes mellitus-pancreatic and cerebellar agenesis syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: G2P, Ambry Genetics, Genomics England PanelApp, Orphanet, Labcorp Genetics (formerly Invitae), PanelApp Australia
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: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.10203478).

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.265C>A	p.Leu89Ile	missense	Exon 1 of 2	NP_835455.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTF1A	ENST00000376504.4	TSL:1 MANE Select	c.265C>A	p.Leu89Ile	missense	Exon 1 of 2	ENSP00000365687.3
	PTF1A	ENST00000638469.1	TSL:5	c.114+118C>A		intron	N/A	ENSP00000491649.1

Frequencies

GnomAD3 genomes

AF:

0.0000790

AC:

AN:

151856

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000952

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000267

AC:

AN:

11236

AF XY:

0.000141

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000321

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000121

AC:

141

AN:

1162136

Hom.:

Cov.:

AF XY:

0.000136

AC XY:

AN XY:

559060

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

23592

American (AMR)

AF:

0.00

AC:

AN:

10242

Ashkenazi Jewish (ASJ)

AF:

0.000124

AC:

AN:

16154

East Asian (EAS)

AF:

0.00

AC:

AN:

26846

South Asian (SAS)

AF:

0.000155

AC:

AN:

38664

European-Finnish (FIN)

AF:

0.000270

AC:

AN:

25940

Middle Eastern (MID)

AF:

0.000265

AC:

AN:

3778

European-Non Finnish (NFE)

AF:

0.000124

AC:

120

AN:

969440

Other (OTH)

AF:

0.000105

AC:

AN:

47480

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.0000790

AC:

AN:

151856

Hom.:

Cov.:

AF XY:

0.0000809

AC XY:

AN XY:

74162

show subpopulations

African (AFR)

AF:

0.0000483

AC:

AN:

41416

American (AMR)

AF:

0.0000656

AC:

AN:

15250

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5152

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.0000952

AC:

AN:

10508

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.000118

AC:

AN:

67916

Other (OTH)

AF:

0.00

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

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:

0.00

Hom.:

Bravo

AF:

0.0000529

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

Monogenic diabetes (1)

not provided (1)

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

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.36

CADD

Benign

7.9

(source)

DANN

Benign

0.85

DEOGEN2

Benign

0.10

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.27

M_CAP

Pathogenic

0.39

MetaRNN

Benign

0.10

MetaSVM

Benign

-0.44

MutationAssessor

Benign

0.0

PhyloP100

0.079

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-0.25

REVEL

Benign

0.16

Sift

Benign

0.18

Sift4G

Benign

0.23

Polyphen

0.0040

Vest4

0.072

MutPred

0.26

Loss of glycosylation at P84 (P = 0.1886)

MVP

0.40

ClinPred

0.0095

GERP RS

-0.27

PromoterAI

-0.041

Neutral

(source)

Varity_R

0.10

gMVP

0.19

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