rs755164485

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000729.6(CCK):​c.325G>T​(p.Glu109*) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,724 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CCK
NM_000729.6 stop_gained

Scores

5
1
1

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.57
Variant links:
Genes affected
CCK (HGNC:1569): (cholecystokinin) This gene encodes a member of the gastrin/cholecystokinin family of proteins. The encoded preproprotein is proteolytically processed to generate multiple protein products, including the peptide hormones cholecystokinin-8, -12, -33, and others. The encoded peptides have been shown to regulate gastric acid secretion and food intake. A sulfated form of cholecystokinin-8 may modulate neuronal activity in the brain. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2015]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CCKNM_000729.6 linkc.325G>T p.Glu109* stop_gained Exon 5 of 5 ENST00000396169.7 NP_000720.1 P06307Q6FG82
CCKNM_001174138.3 linkc.325G>T p.Glu109* stop_gained Exon 3 of 3 NP_001167609.1 P06307Q6FG82

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CCKENST00000396169.7 linkc.325G>T p.Glu109* stop_gained Exon 5 of 5 1 NM_000729.6 ENSP00000379472.2 P06307
CCKENST00000334681.9 linkc.325G>T p.Glu109* stop_gained Exon 3 of 3 1 ENSP00000335657.5 P06307
CCKENST00000434608.1 linkc.325G>T p.Glu109* stop_gained Exon 3 of 3 1 ENSP00000409124.1 P06307

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461724
Hom.:
0
Cov.:
30
AF XY:
0.00000138
AC XY:
1
AN XY:
727154
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.62
D
BayesDel_noAF
Pathogenic
0.66
CADD
Pathogenic
41
DANN
Uncertain
1.0
Eigen
Pathogenic
1.2
Eigen_PC
Pathogenic
1.1
FATHMM_MKL
Pathogenic
0.99
D
Vest4
0.93
GERP RS
5.7

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: chr3-42299613; API