X-49063927-C-T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2

The NM_001163321.4(CCDC120):​c.355C>T​(p.Arg119Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000306 in 1,207,402 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 16 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., 1 hem., cov: 23)
Exomes 𝑓: 0.000031 ( 0 hom. 15 hem. )

Consequence

CCDC120
NM_001163321.4 missense

Scores

4
9
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.662
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 -3 ACMG points.

PP3
MetaRNN computational evidence supports a deleterious effect, 0.762
BS2
High Hemizygotes in GnomAdExome4 at 15 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CCDC120NM_001163321.4 linkc.355C>T p.Arg119Trp 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.355C>T p.Arg119Trp missense_variant Exon 5 of 11 2 NM_001163321.4 ENSP00000474071.1 Q96HB5-4

Frequencies

GnomAD3 genomes
AF:
0.0000270
AC:
3
AN:
111176
Hom.:
0
Cov.:
23
AF XY:
0.0000300
AC XY:
1
AN XY:
33362
show subpopulations
Gnomad AFR
AF:
0.0000327
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000956
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:
0.0000189
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000172
AC:
3
AN:
174498
Hom.:
0
AF XY:
0.0000163
AC XY:
1
AN XY:
61406
show subpopulations
Gnomad AFR exome
AF:
0.0000808
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000546
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000130
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000310
AC:
34
AN:
1096226
Hom.:
0
Cov.:
31
AF XY:
0.0000415
AC XY:
15
AN XY:
361810
show subpopulations
Gnomad4 AFR exome
AF:
0.000190
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000309
Gnomad4 OTH exome
AF:
0.0000653
GnomAD4 genome
AF:
0.0000270
AC:
3
AN:
111176
Hom.:
0
Cov.:
23
AF XY:
0.0000300
AC XY:
1
AN XY:
33362
show subpopulations
Gnomad4 AFR
AF:
0.0000327
Gnomad4 AMR
AF:
0.0000956
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000189
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000340
ExAC
AF:
0.00000825
AC:
1

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Oct 18, 2021
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.250C>T (p.R84W) 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 250, causing the arginine (R) at amino acid position 84 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
0.22
BayesDel_addAF
Uncertain
0.023
T
BayesDel_noAF
Uncertain
-0.010
CADD
Uncertain
25
DANN
Pathogenic
1.0
DEOGEN2
Uncertain
0.51
D;D;D;.;.
FATHMM_MKL
Uncertain
0.78
D
LIST_S2
Uncertain
0.93
.;.;D;D;D
M_CAP
Benign
0.076
D
MetaRNN
Pathogenic
0.76
D;D;D;D;D
MetaSVM
Uncertain
-0.23
T
MutationAssessor
Uncertain
2.6
M;M;M;.;.
PrimateAI
Uncertain
0.71
T
PROVEAN
Pathogenic
-7.1
.;.;.;.;D
REVEL
Benign
0.12
Sift
Pathogenic
0.0
.;.;.;.;D
Sift4G
Uncertain
0.0070
D;D;D;D;D
Polyphen
1.0
D;D;D;.;.
Vest4
0.72
MutPred
0.45
Gain of catalytic residue at P87 (P = 0.0428);Gain of catalytic residue at P87 (P = 0.0428);Gain of catalytic residue at P87 (P = 0.0428);.;.;
MVP
0.36
ClinPred
0.97
D
GERP RS
3.7
Varity_R
0.66
gMVP
0.71

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: rs782132519; hg19: chrX-48921458; COSMIC: COSV64515487; COSMIC: COSV64515487; API