3-12807448-C-T

Variant summary

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

The NM_001162499.2(CAND2):​c.355C>T​(p.Pro119Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,399,238 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P119A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

CAND2
NM_001162499.2 missense

Scores

1
18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.28
Variant links:
Genes affected
CAND2 (HGNC:30689): (cullin associated and neddylation dissociated 2 (putative)) Predicted to enable TBP-class protein binding activity. Predicted to be involved in SCF complex assembly; positive regulation of transcription, DNA-templated; and protein ubiquitination. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

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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=0.1003764).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CAND2NM_001162499.2 linkc.355C>T p.Pro119Ser missense_variant Exon 3 of 15 ENST00000456430.6 NP_001155971.1 O75155-1
CAND2XM_011533504.3 linkc.283C>T p.Pro95Ser missense_variant Exon 3 of 15 XP_011531806.1
CAND2XM_011533503.3 linkc.355C>T p.Pro119Ser missense_variant Exon 3 of 14 XP_011531805.1
CAND2NM_012298.3 linkc.213-2611C>T intron_variant Intron 2 of 12 NP_036430.1 O75155-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CAND2ENST00000456430.6 linkc.355C>T p.Pro119Ser missense_variant Exon 3 of 15 1 NM_001162499.2 ENSP00000387641.2 O75155-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
7.15e-7
AC:
1
AN:
1399238
Hom.:
0
Cov.:
35
AF XY:
0.00
AC XY:
0
AN XY:
690120
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:
9.27e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.077
BayesDel_addAF
Benign
-0.24
T
BayesDel_noAF
Benign
-0.58
CADD
Benign
8.4
DANN
Benign
0.96
DEOGEN2
Benign
0.016
T
Eigen
Benign
-0.80
Eigen_PC
Benign
-0.69
FATHMM_MKL
Benign
0.74
D
LIST_S2
Uncertain
0.94
D
M_CAP
Benign
0.024
T
MetaRNN
Benign
0.10
T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
1.4
L
PrimateAI
Benign
0.47
T
PROVEAN
Benign
-1.9
N
REVEL
Benign
0.061
Sift
Benign
0.19
T
Sift4G
Benign
0.61
T
Polyphen
0.0030
B
Vest4
0.070
MutPred
0.65
Loss of catalytic residue at P118 (P = 0.0171);
MVP
0.28
MPC
1.1
ClinPred
0.065
T
GERP RS
2.6
Varity_R
0.050
gMVP
0.15

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: chr3-12848947; API