X-49063961-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001163321.4(CCDC120):​c.389C>T​(p.Pro130Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000332 in 1,205,207 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 6 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/19 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. P130A) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000036 ( 0 hom., 0 hem., cov: 23)
Exomes 𝑓: 0.000033 ( 0 hom. 6 hem. )

Consequence

CCDC120
NM_001163321.4 missense

Scores

1
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.410
Variant links:
Genes affected
CCDC120 (HGNC:28910): (coiled-coil domain containing 120) This gene encodes a protein that contains a coiled-coil domain. Several alternatively spliced transcript variants encoding multiple isoforms have been found for this gene. [provided by RefSeq, Nov 2012]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.008878529).
BS2
High Hemizygotes in GnomAdExome4 at 6 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CCDC120NM_001163321.4 linkc.389C>T p.Pro130Leu missense_variant Exon 5 of 11 ENST00000603986.6 NP_001156793.2 Q96HB5-4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CCDC120ENST00000603986.6 linkc.389C>T p.Pro130Leu missense_variant Exon 5 of 11 2 NM_001163321.4 ENSP00000474071.1 Q96HB5-4

Frequencies

GnomAD3 genomes
AF:
0.0000360
AC:
4
AN:
111023
Hom.:
0
Cov.:
23
AF XY:
0.00
AC XY:
0
AN XY:
33219
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00113
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:
0.0000937
AC:
16
AN:
170814
Hom.:
0
AF XY:
0.0000519
AC XY:
3
AN XY:
57844
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000380
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000763
Gnomad SAS exome
AF:
0.000226
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000237
GnomAD4 exome
AF:
0.0000329
AC:
36
AN:
1094184
Hom.:
0
Cov.:
31
AF XY:
0.0000167
AC XY:
6
AN XY:
360036
show subpopulations
Gnomad4 AFR exome
AF:
0.000114
Gnomad4 AMR exome
AF:
0.0000288
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000333
Gnomad4 SAS exome
AF:
0.000168
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000107
Gnomad4 OTH exome
AF:
0.0000872
GnomAD4 genome
AF:
0.0000360
AC:
4
AN:
111023
Hom.:
0
Cov.:
23
AF XY:
0.00
AC XY:
0
AN XY:
33219
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00113
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000529
ExAC
AF:
0.0000907
AC:
11

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Feb 06, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.284C>T (p.P95L) alteration is located in exon 5 (coding exon 3) of the CCDC120 gene. This alteration results from a C to T substitution at nucleotide position 284, causing the proline (P) at amino acid position 95 to be replaced by a leucine (L). 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
0.067
BayesDel_addAF
Benign
-0.56
T
BayesDel_noAF
Benign
-0.67
CADD
Benign
8.5
DANN
Benign
0.78
DEOGEN2
Benign
0.0041
T;T;T;.;.
FATHMM_MKL
Benign
0.049
N
LIST_S2
Benign
0.73
.;.;T;T;T
M_CAP
Benign
0.0034
T
MetaRNN
Benign
0.0089
T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-0.90
N;N;N;.;.
PrimateAI
Benign
0.44
T
PROVEAN
Benign
0.63
.;.;.;.;N
REVEL
Benign
0.030
Sift
Benign
0.35
.;.;.;.;T
Sift4G
Uncertain
0.014
D;D;D;D;D
Polyphen
0.0
B;B;B;.;.
Vest4
0.099
MVP
0.043
ClinPred
0.016
T
GERP RS
1.3
Varity_R
0.035
gMVP
0.51

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: rs781809137; hg19: chrX-48921492; API