10-118754708-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_153810.5(CACUL1):​c.55G>A​(p.Asp19Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000374 in 1,606,166 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

CACUL1
NM_153810.5 missense

Scores

4
2
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.47
Variant links:
Genes affected
CACUL1 (HGNC:23727): (CDK2 associated cullin domain 1) Enables protein kinase binding activity. Involved in G1/S transition of mitotic cell cycle; positive regulation of cell population proliferation; and positive regulation of protein kinase activity. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.16589236).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CACUL1NM_153810.5 linkc.55G>A p.Asp19Asn missense_variant Exon 1 of 9 ENST00000369151.8 NP_722517.3 Q86Y37-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CACUL1ENST00000369151.8 linkc.55G>A p.Asp19Asn missense_variant Exon 1 of 9 1 NM_153810.5 ENSP00000358147.2 Q86Y37-1
CACUL1ENST00000493518.5 linkn.55G>A non_coding_transcript_exon_variant Exon 1 of 10 1 ENSP00000431329.1 Q86Y37-2
CACUL1ENST00000477583.1 linkn.-231G>A upstream_gene_variant 1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152166
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000835
AC:
2
AN:
239412
Hom.:
0
AF XY:
0.00000766
AC XY:
1
AN XY:
130628
show subpopulations
Gnomad AFR exome
AF:
0.000147
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000344
AC:
5
AN:
1454000
Hom.:
0
Cov.:
32
AF XY:
0.00000553
AC XY:
4
AN XY:
723512
show subpopulations
Gnomad4 AFR exome
AF:
0.0000625
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:
0.0000166
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152166
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74330
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756
ExAC
AF:
0.0000165
AC:
2

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 21, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.55G>A (p.D19N) alteration is located in exon 1 (coding exon 1) of the CACUL1 gene. This alteration results from a G to A substitution at nucleotide position 55, causing the aspartic acid (D) at amino acid position 19 to be replaced by an asparagine (N). 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
Pathogenic
0.86
BayesDel_addAF
Benign
-0.33
T
BayesDel_noAF
Benign
-0.46
CADD
Pathogenic
29
DANN
Uncertain
1.0
DEOGEN2
Benign
0.050
T
Eigen
Benign
-0.17
Eigen_PC
Benign
-0.0062
FATHMM_MKL
Benign
0.69
D
LIST_S2
Benign
0.85
T
M_CAP
Uncertain
0.14
D
MetaRNN
Benign
0.17
T
MetaSVM
Benign
-0.87
T
MutationAssessor
Benign
1.4
L
PrimateAI
Pathogenic
0.81
D
PROVEAN
Benign
-1.3
N
REVEL
Benign
0.060
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0
D
Polyphen
0.013
B
Vest4
0.52
MutPred
0.40
Gain of helix (P = 0.0854);
MVP
0.14
MPC
1.1
ClinPred
0.74
D
GERP RS
3.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.51
gMVP
0.53

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.

Other links and lift over

dbSNP: rs779236291; hg19: chr10-120514220; API