rs769216699
Positions:
Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_001379610.1(SPINK1):āc.111T>Cā(p.Asn37=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000601 in 1,613,236 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.000046 ( 0 hom., cov: 32)
Exomes š: 0.000062 ( 0 hom. )
Consequence
SPINK1
NM_001379610.1 synonymous
NM_001379610.1 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.200
Genes affected
SPINK1 (HGNC:11244): (serine peptidase inhibitor Kazal type 1) The protein encoded by this gene is a trypsin inhibitor, which is secreted from pancreatic acinar cells into pancreatic juice. It is thought to function in the prevention of trypsin-catalyzed premature activation of zymogens within the pancreas and the pancreatic duct. Mutations in this gene are associated with hereditary pancreatitis and tropical calcific pancreatitis. [provided by RefSeq, Oct 2008]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -17 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BP6
?
Variant 5-147828105-A-G is Benign according to our data. Variant chr5-147828105-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 528774.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.2 with no splicing effect.
BS2
?
High AC in GnomAd4 at 7 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SPINK1 | NM_001379610.1 | c.111T>C | p.Asn37= | synonymous_variant | 3/4 | ENST00000296695.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SPINK1 | ENST00000296695.10 | c.111T>C | p.Asn37= | synonymous_variant | 3/4 | 1 | NM_001379610.1 | P1 | |
SPINK1 | ENST00000510027.2 | c.111T>C | p.Asn37= | synonymous_variant | 3/3 | 3 | |||
SPINK1 | ENST00000505722.1 | n.26T>C | non_coding_transcript_exon_variant | 1/2 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000460 AC: 7AN: 152224Hom.: 0 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
7
AN:
152224
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0000560 AC: 14AN: 250044Hom.: 0 AF XY: 0.0000444 AC XY: 6AN XY: 135152
GnomAD3 exomes
AF:
AC:
14
AN:
250044
Hom.:
AF XY:
AC XY:
6
AN XY:
135152
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000616 AC: 90AN: 1461012Hom.: 0 Cov.: 30 AF XY: 0.0000509 AC XY: 37AN XY: 726796
GnomAD4 exome
AF:
AC:
90
AN:
1461012
Hom.:
Cov.:
30
AF XY:
AC XY:
37
AN XY:
726796
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.0000460 AC: 7AN: 152224Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74368
GnomAD4 genome
?
AF:
AC:
7
AN:
152224
Hom.:
Cov.:
32
AF XY:
AC XY:
4
AN XY:
74368
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Hereditary pancreatitis Benign:3
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 23, 2018 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Oct 26, 2023 | - - |
Likely benign, criteria provided, single submitter | curation | Sema4, Sema4 | Dec 27, 2020 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at