X-49065519-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001163321.4(CCDC120):​c.853C>T​(p.Arg285Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000207 in 1,208,937 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 7 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., 0 hem., cov: 24)
Exomes 𝑓: 0.000020 ( 0 hom. 7 hem. )

Consequence

CCDC120
NM_001163321.4 missense

Scores

1
7
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.28
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 Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.13163754).
BS2
High Hemizygotes in GnomAdExome4 at 7 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CCDC120NM_001163321.4 linkc.853C>T p.Arg285Trp missense_variant Exon 8 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.853C>T p.Arg285Trp missense_variant Exon 8 of 11 2 NM_001163321.4 ENSP00000474071.1 Q96HB5-4

Frequencies

GnomAD3 genomes
AF:
0.0000267
AC:
3
AN:
112524
Hom.:
0
Cov.:
24
AF XY:
0.00
AC XY:
0
AN XY:
34660
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:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000564
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000681
AC:
12
AN:
176334
Hom.:
0
AF XY:
0.0000485
AC XY:
3
AN XY:
61912
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000747
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000738
Gnomad SAS exome
AF:
0.0000553
Gnomad FIN exome
AF:
0.0000645
Gnomad NFE exome
AF:
0.0000894
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000201
AC:
22
AN:
1096413
Hom.:
0
Cov.:
32
AF XY:
0.0000193
AC XY:
7
AN XY:
361905
show subpopulations
Gnomad4 AFR exome
AF:
0.0000379
Gnomad4 AMR exome
AF:
0.000114
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000331
Gnomad4 SAS exome
AF:
0.0000186
Gnomad4 FIN exome
AF:
0.0000247
Gnomad4 NFE exome
AF:
0.0000155
Gnomad4 OTH exome
AF:
0.0000217
GnomAD4 genome
AF:
0.0000267
AC:
3
AN:
112524
Hom.:
0
Cov.:
24
AF XY:
0.00
AC XY:
0
AN XY:
34660
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000564
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000340
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000149
AC:
1
ExAC
AF:
0.0000659
AC:
8

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jan 09, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.748C>T (p.R250W) alteration is located in exon 8 (coding exon 6) of the CCDC120 gene. This alteration results from a C to T substitution at nucleotide position 748, causing the arginine (R) at amino acid position 250 to be replaced by a tryptophan (W). 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
0.17
BayesDel_addAF
Benign
-0.095
T
BayesDel_noAF
Benign
-0.18
CADD
Benign
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.24
T;T;T;.;.
FATHMM_MKL
Uncertain
0.77
D
LIST_S2
Uncertain
0.86
.;.;D;D;D
M_CAP
Benign
0.045
D
MetaRNN
Benign
0.13
T;T;T;T;T
MetaSVM
Benign
-0.85
T
MutationAssessor
Uncertain
2.3
M;M;M;.;.
PrimateAI
Uncertain
0.74
T
PROVEAN
Uncertain
-3.5
.;.;.;.;D
REVEL
Benign
0.20
Sift
Pathogenic
0.0
.;.;.;.;D
Sift4G
Uncertain
0.015
D;D;D;D;D
Polyphen
0.0040
B;B;B;.;.
Vest4
0.10
MVP
0.14
ClinPred
0.22
T
GERP RS
4.2
Varity_R
0.61
gMVP
0.42

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: rs373973921; hg19: chrX-48923050; API