2-27627022-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_024584.5(CCDC121):​c.778G>A​(p.Val260Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000867 in 1,613,900 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 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: 32)
Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

CCDC121
NM_024584.5 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0300
Variant links:
Genes affected
CCDC121 (HGNC:25833): (coiled-coil domain containing 121)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.028909802).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CCDC121NM_024584.5 linkc.778G>A p.Val260Ile missense_variant Exon 2 of 2 ENST00000324364.4 NP_078860.2 Q6ZUS5-1
CCDC121NM_001142683.3 linkc.1264G>A p.Val422Ile missense_variant Exon 2 of 2 NP_001136155.1 Q6ZUS5-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CCDC121ENST00000324364.4 linkc.778G>A p.Val260Ile missense_variant Exon 2 of 2 1 NM_024584.5 ENSP00000339087.2 Q6ZUS5-1
CCDC121ENST00000394775.3 linkc.1264G>A p.Val422Ile missense_variant Exon 2 of 2 1 ENSP00000412150.2 Q6ZUS5-2
ENSG00000259080ENST00000505973.1 linkn.1389-2837C>T intron_variant Intron 12 of 17 2

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152236
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000192
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:
0.0000279
AC:
7
AN:
251186
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135756
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000381
Gnomad SAS 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:
0.00000821
AC:
12
AN:
1461664
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
727122
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000202
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152236
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74370
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000192
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
ExAC
AF:
0.0000330
AC:
4

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Dec 04, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1264G>A (p.V422I) alteration is located in exon 2 (coding exon 2) of the CCDC121 gene. This alteration results from a G to A substitution at nucleotide position 1264, causing the valine (V) at amino acid position 422 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
0.087
BayesDel_addAF
Benign
-0.57
T
BayesDel_noAF
Benign
-0.74
CADD
Benign
9.6
DANN
Benign
0.48
DEOGEN2
Benign
0.021
T;.
Eigen
Benign
-0.89
Eigen_PC
Benign
-0.95
FATHMM_MKL
Benign
0.011
N
LIST_S2
Benign
0.47
T;T
M_CAP
Benign
0.0047
T
MetaRNN
Benign
0.029
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.34
N;.
PrimateAI
Benign
0.25
T
PROVEAN
Benign
-0.52
N;N
REVEL
Benign
0.037
Sift
Benign
0.33
T;T
Sift4G
Benign
0.26
T;T
Polyphen
0.19
B;.
Vest4
0.043
MutPred
0.081
Gain of methylation at K262 (P = 0.1166);.;
MVP
0.22
MPC
0.18
ClinPred
0.036
T
GERP RS
0.62
Varity_R
0.038
gMVP
0.0088

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: rs756637183; hg19: chr2-27849889; API