2-196646371-G-A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001080539.2(CCDC150):​c.43G>A​(p.Val15Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000806 in 1,613,680 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V15A) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

CCDC150
NM_001080539.2 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.634

Publications

0 publications found
Variant links:
Genes affected
CCDC150 (HGNC:26834): (coiled-coil domain containing 150)

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.08585361).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CCDC150NM_001080539.2 linkc.43G>A p.Val15Ile missense_variant Exon 2 of 28 ENST00000389175.9 NP_001074008.1 Q8NCX0-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CCDC150ENST00000389175.9 linkc.43G>A p.Val15Ile missense_variant Exon 2 of 28 5 NM_001080539.2 ENSP00000373827.4 Q8NCX0-1

Frequencies

GnomAD3 genomes
AF:
0.0000526
AC:
8
AN:
152132
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000169
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
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:
0.0000120
AC:
3
AN:
249174
AF XY:
0.00000740
show subpopulations
Gnomad AFR exome
AF:
0.000194
Gnomad AMR exome
AF:
0.00
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:
0.00000342
AC:
5
AN:
1461548
Hom.:
0
Cov.:
30
AF XY:
0.00000275
AC XY:
2
AN XY:
727056
show subpopulations
African (AFR)
AF:
0.0000896
AC:
3
AN:
33476
American (AMR)
AF:
0.00
AC:
0
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26128
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39690
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86250
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53402
Middle Eastern (MID)
AF:
0.000173
AC:
1
AN:
5768
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1111740
Other (OTH)
AF:
0.0000166
AC:
1
AN:
60370
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.445
Heterozygous variant carriers
0
1
1
2
2
3
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:
0.0000526
AC:
8
AN:
152132
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74314
show subpopulations
African (AFR)
AF:
0.000169
AC:
7
AN:
41428
American (AMR)
AF:
0.0000655
AC:
1
AN:
15264
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3470
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5198
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4826
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10600
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
68028
Other (OTH)
AF:
0.00
AC:
0
AN:
2090
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.494
Heterozygous variant carriers
0
1
1
2
2
3
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:
0.0000987
Hom.:
0
Bravo
AF:
0.0000642
ESP6500AA
AF:
0.000515
AC:
2
ESP6500EA
AF:
0.00
AC:
0
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
Sep 26, 2023
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.43G>A (p.V15I) alteration is located in exon 2 (coding exon 2) of the CCDC150 gene. This alteration results from a G to A substitution at nucleotide position 43, causing the valine (V) at amino acid position 15 to be replaced by an isoleucine (I). 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
0.094
BayesDel_addAF
Benign
-0.49
T
BayesDel_noAF
Benign
-0.67
CADD
Benign
6.6
DANN
Uncertain
1.0
DEOGEN2
Benign
0.0051
T
Eigen
Benign
-0.099
Eigen_PC
Benign
-0.22
FATHMM_MKL
Benign
0.079
N
LIST_S2
Benign
0.65
T
M_CAP
Benign
0.0043
T
MetaRNN
Benign
0.086
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.5
L
PhyloP100
0.63
PrimateAI
Benign
0.34
T
PROVEAN
Benign
-0.30
N
REVEL
Benign
0.057
Sift
Benign
0.29
T
Sift4G
Benign
0.28
T
Polyphen
0.71
P
Vest4
0.19
MVP
0.030
MPC
0.032
ClinPred
0.12
T
GERP RS
2.7
Varity_R
0.023
gMVP
0.11
Mutation Taster
=94/6
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: rs372552459; hg19: chr2-197511095; API