10-23192612-A-C

Position:

• chr10-23192612-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_178161.3(PTF1A):​c.82A>C​(p.Thr28Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PTF1A NM_178161.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.17

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35764432).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTF1A	NM_178161.3	c.82A>C	p.Thr28Pro	missense_variant	1/2	ENST00000376504.4	NP_835455.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTF1A	ENST00000376504.4	c.82A>C	p.Thr28Pro	missense_variant	1/2	1	NM_178161.3	ENSP00000365687.3
PTF1A	ENST00000638469.1	c.49A>C	p.Thr17Pro	missense_variant	1/2	5		ENSP00000491649.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 25, 2023

The c.82A>C (p.T28P) alteration is located in exon 1 (coding exon 1) of the PTF1A gene. This alteration results from a A to C substitution at nucleotide position 82, causing the threonine (T) at amino acid position 28 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.060
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.27	T;.
Eigen	Benign	0.15
Eigen_PC	Benign	0.081
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.53	T;T
M_CAP	Pathogenic	0.55	D
MetaRNN	Benign	0.36	T;T
MetaSVM	Uncertain	0.77	D
MutationAssessor	Benign	1.9	L;.
PrimateAI	Pathogenic	0.80	T
PROVEAN	Uncertain	-2.6	D;.
REVEL	Uncertain	0.58
Sift	Uncertain	0.0010	D;.
Sift4G	Uncertain	0.014	D;.
Polyphen		0.99	D;.
Vest4		0.44
MutPred		0.12		Loss of phosphorylation at T28 (P = 0.03);.;
MVP		0.80
ClinPred		0.96	D
GERP RS		3.0
Varity_R		0.66
gMVP		0.28

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-23481541;