10-23192692-C-T

Position:

chr10-23192692-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_178161.3(PTF1A):c.162C>T(p.Ser54Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0029 in 1,588,030 control chromosomes in the GnomAD database, including 118 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0025 ( 7 hom., cov: 32)

Exomes 𝑓: 0.0029 ( 111 hom. )

Consequence

PTF1A
NM_178161.3 synonymous

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:2

Conservation

PhyloP100: 1.61

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP6

Variant 10-23192692-C-T is Benign according to our data. Variant chr10-23192692-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 299622.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1, Benign=1}.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00254 (386/152166) while in subpopulation EAS AF= 0.0365 (188/5154). AF 95% confidence interval is 0.0322. There are 7 homozygotes in gnomad4. There are 249 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTF1A	NM_178161.3 linkuse as main transcript	c.162C>T	p.Ser54Ser	synonymous_variant	1/2	ENST00000376504.4	NP_835455.1	Q7RTS3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTF1A	ENST00000376504.4 linkuse as main transcript	c.162C>T	p.Ser54Ser	synonymous_variant	1/2	1	NM_178161.3	ENSP00000365687.3		Q7RTS3
PTF1A	ENST00000638469.1 linkuse as main transcript	c.114+15C>T		intron_variant		5		ENSP00000491649.1		A0A1W2PQC4

Frequencies

GnomAD3 genomes

AF:

0.00253

AC:

385

AN:

152056

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000410

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0362

Gnomad SAS

AF:

0.0342

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00734

AC:

1609

AN:

219074

Hom.:

AF XY:

0.00829

AC XY:

1000

AN XY:

120606

show subpopulations

Gnomad AFR exome

AF:

0.000313

Gnomad AMR exome

AF:

0.000287

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0398

Gnomad SAS exome

AF:

0.0344

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000499

Gnomad OTH exome

AF:

0.00474

GnomAD4 exome

AF:

0.00294

AC:

4221

AN:

1435864

Hom.:

111

Cov.:

AF XY:

0.00375

AC XY:

2677

AN XY:

714432

show subpopulations

Gnomad4 AFR exome

AF:

0.000224

Gnomad4 AMR exome

AF:

0.000187

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0313

Gnomad4 SAS exome

AF:

0.0326

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000281

Gnomad4 OTH exome

AF:

0.00463

GnomAD4 genome

AF:

0.00254

AC:

386

AN:

152166

Hom.:

Cov.:

AF XY:

0.00335

AC XY:

249

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.000409

Gnomad4 AMR

AF:

0.000458

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0365

Gnomad4 SAS

AF:

0.0342

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000589

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.000967

Hom.:

Bravo

AF:

0.00181

Asia WGS

AF:

0.0280

AC:

AN:

3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Neonatal insulin-dependent diabetes mellitus

Uncertain:1

Uncertain significance, criteria provided, single submitter

research

Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic

PTF1A gene is associated with neonatal onset diabetes due to pancreatic aplasia, leading to insulin dependence. It is associated with extra pancreatic manifestation of neurological impairment. However, the role of this particulat variant (rs117678424) in neonatal diabetes is yet to be ascertained. -

Permanent neonatal diabetes mellitus-pancreatic and cerebellar agenesis syndrome

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Uncertain

0.98

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

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