rs1554799853

Variant names:

• chr10-23193694-A-C
• rs1554799853
• NM_178161.3:c.785-10A>C

Your query was ambiguous. Multiple possible variants found:

• chr10-23193694-A-C
• chr10-23193694-A-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_178161.3(PTF1A):​c.785-10A>C variant causes a intron 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. There are indicators that this mutation may affect the branch point..

• Frequency: Genomes: not found (cov: 31)
• Consequence: PTF1A NM_178161.3 intron
• Scores: Splicing: ADA: 0.00001184
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.174
• Publications: 0 publications found

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 3 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.84).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTF1A	NM_178161.3	MANE Select	c.785-10A>C		intron	N/A	NP_835455.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTF1A	ENST00000376504.4	TSL:1 MANE Select	c.785-10A>C		intron	N/A	ENSP00000365687.3
	PTF1A	ENST00000639082.1	TSL:5	c.44-58A>C		intron	N/A	ENSP00000492481.1
	PTF1A	ENST00000638469.1	TSL:5	c.115-10A>C		intron	N/A	ENSP00000491649.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 26

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.2
DANN	Benign	0.71
PhyloP100		-0.17
BranchPoint Hunter		3.0
PromoterAI		0.093	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000012
dbscSNV1_RF	Benign	0.0060
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

Other links and lift over

dbSNP: rs1554799853; hg19: chr10-23482623;