chr22-21634299-T-A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_152612.3(CCDC116):​c.350T>A​(p.Val117Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000682 in 1,612,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

CCDC116
NM_152612.3 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.358

Publications

0 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: Likely_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.051700085).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CCDC116NM_152612.3 linkc.350T>A p.Val117Glu 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.350T>A p.Val117Glu missense_variant Exon 3 of 5 1 NM_152612.3 ENSP00000292779.3 Q8IYX3-2
CCDC116ENST00000607942.5 linkc.350T>A p.Val117Glu missense_variant Exon 3 of 4 2 ENSP00000476296.1 Q8IYX3-3
CCDC116ENST00000425975.1 linkc.*90T>A downstream_gene_variant 4 ENSP00000401637.1 C9JW89

Frequencies

GnomAD3 genomes
AF:
0.0000132
AC:
2
AN:
151902
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
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
GnomAD2 exomes
AF:
0.0000320
AC:
8
AN:
249850
AF XY:
0.0000148
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000232
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:
0.00000616
AC:
9
AN:
1460990
Hom.:
0
Cov.:
34
AF XY:
0.00000275
AC XY:
2
AN XY:
726820
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33480
American (AMR)
AF:
0.000179
AC:
8
AN:
44704
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26120
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39694
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86234
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
52670
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
8.99e-7
AC:
1
AN:
1111936
Other (OTH)
AF:
0.00
AC:
0
AN:
60384
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.503
Heterozygous variant carriers
0
1
2
3
4
5
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.0000132
AC:
2
AN:
151902
Hom.:
0
Cov.:
33
AF XY:
0.0000270
AC XY:
2
AN XY:
74196
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
41340
American (AMR)
AF:
0.000131
AC:
2
AN:
15264
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3470
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5172
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4816
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10572
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
67950
Other (OTH)
AF:
0.00
AC:
0
AN:
2092
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.00000378
ExAC
AF:
0.0000247
AC:
3

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Apr 10, 2025
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.350T>A (p.V117E) alteration is located in exon 3 (coding exon 2) of the CCDC116 gene. This alteration results from a T to A substitution at nucleotide position 350, causing the valine (V) at amino acid position 117 to be replaced by a glutamic acid (E). 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
Benign
0.14
BayesDel_addAF
Benign
-0.36
T
BayesDel_noAF
Benign
-0.46
CADD
Benign
14
DANN
Benign
0.96
DEOGEN2
Benign
0.014
.;T
Eigen
Benign
-0.82
Eigen_PC
Benign
-0.91
FATHMM_MKL
Benign
0.055
N
LIST_S2
Benign
0.48
T;T
M_CAP
Benign
0.0091
T
MetaRNN
Benign
0.052
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.5
L;L
PhyloP100
-0.36
PrimateAI
Benign
0.38
T
PROVEAN
Uncertain
-3.6
.;D
REVEL
Benign
0.016
Sift
Benign
0.10
.;T
Sift4G
Benign
0.10
T;T
Vest4
0.15
MutPred
0.44
Loss of sheet (P = 0.0084);Loss of sheet (P = 0.0084);
MVP
0.12
MPC
0.36
ClinPred
0.060
T
GERP RS
-0.41
Varity_R
0.22
gMVP
0.11
Mutation Taster
=98/2
polymorphism

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

Other links and lift over

dbSNP: rs753258845; hg19: chr22-21988588; API