rs781434365

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_152612.3(CCDC116):​c.367C>G​(p.Arg123Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,110 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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. R123W) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CCDC116
NM_152612.3 missense

Scores

2
2
15

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.240

Publications

1 publications found
Variant links:
Genes affected
CCDC116 (HGNC:26688): (coiled-coil domain containing 116) Located in centrosome. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.2746535).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CCDC116NM_152612.3 linkc.367C>G p.Arg123Gly missense_variant Exon 3 of 5 ENST00000292779.4 NP_689825.2 Q8IYX3-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CCDC116ENST00000292779.4 linkc.367C>G p.Arg123Gly missense_variant Exon 3 of 5 1 NM_152612.3 ENSP00000292779.3 Q8IYX3-2
CCDC116ENST00000607942.5 linkc.367C>G p.Arg123Gly missense_variant Exon 3 of 4 2 ENSP00000476296.1 Q8IYX3-3
CCDC116ENST00000425975.1 linkc.*107C>G downstream_gene_variant 4 ENSP00000401637.1 C9JW89

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD2 exomes
AF:
0.00000402
AC:
1
AN:
248710
AF XY:
0.00
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000290
Gnomad ASJ exome
AF:
0.00
Gnomad EAS 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:
6.85e-7
AC:
1
AN:
1460110
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
726372
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33472
American (AMR)
AF:
0.0000224
AC:
1
AN:
44670
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26084
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39688
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86180
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
52164
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5766
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1111712
Other (OTH)
AF:
0.00
AC:
0
AN:
60374
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.16
BayesDel_addAF
Benign
-0.15
T
BayesDel_noAF
Benign
-0.37
CADD
Benign
16
DANN
Uncertain
0.98
DEOGEN2
Benign
0.031
.;T
Eigen
Benign
-0.14
Eigen_PC
Benign
-0.32
FATHMM_MKL
Benign
0.12
N
LIST_S2
Benign
0.73
T;T
M_CAP
Benign
0.010
T
MetaRNN
Benign
0.27
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.8
L;L
PhyloP100
0.24
PrimateAI
Benign
0.33
T
PROVEAN
Pathogenic
-5.8
.;D
REVEL
Benign
0.11
Sift
Uncertain
0.0040
.;D
Sift4G
Pathogenic
0.0
D;D
Vest4
0.37
MutPred
0.41
Loss of methylation at R123 (P = 0.0179);Loss of methylation at R123 (P = 0.0179);
MVP
0.38
MPC
0.81
ClinPred
0.98
D
GERP RS
3.3
Varity_R
0.26
gMVP
0.16
Mutation Taster
=91/9
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs781434365; hg19: chr22-21988605; API