2-27627394-C-A

Variant summary

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

The NM_024584.5(CCDC121):​c.406G>T​(p.Ala136Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 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. A136V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

CCDC121
NM_024584.5 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.184
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=0.06473085).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CCDC121NM_024584.5 linkc.406G>T p.Ala136Ser missense_variant Exon 2 of 2 ENST00000324364.4 NP_078860.2 Q6ZUS5-1
CCDC121NM_001142683.3 linkc.892G>T p.Ala298Ser 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.406G>T p.Ala136Ser missense_variant Exon 2 of 2 1 NM_024584.5 ENSP00000339087.2 Q6ZUS5-1
CCDC121ENST00000394775.3 linkc.892G>T p.Ala298Ser missense_variant Exon 2 of 2 1 ENSP00000412150.2 Q6ZUS5-2
ENSG00000259080ENST00000505973.1 linkn.1389-2465C>A intron_variant Intron 12 of 17 2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
6.84e-7
AC:
1
AN:
1461872
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
727232
show subpopulations
Gnomad4 AFR exome
AF:
0.00
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Feb 16, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.892G>T (p.A298S) alteration is located in exon 2 (coding exon 2) of the CCDC121 gene. This alteration results from a G to T substitution at nucleotide position 892, causing the alanine (A) at amino acid position 298 to be replaced by a serine (S). 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
0.12
BayesDel_addAF
Benign
-0.30
T
BayesDel_noAF
Benign
-0.67
CADD
Benign
2.7
DANN
Benign
0.60
DEOGEN2
Benign
0.017
T;.
Eigen
Benign
-0.72
Eigen_PC
Benign
-0.79
FATHMM_MKL
Benign
0.032
N
LIST_S2
Benign
0.42
T;T
M_CAP
Benign
0.0061
T
MetaRNN
Benign
0.065
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.0
L;.
PrimateAI
Benign
0.27
T
PROVEAN
Benign
-0.58
N;N
REVEL
Benign
0.038
Sift
Benign
0.36
T;T
Sift4G
Benign
0.38
T;T
Polyphen
0.56
P;.
Vest4
0.091
MutPred
0.17
Gain of relative solvent accessibility (P = 0.0023);.;
MVP
0.16
MPC
0.20
ClinPred
0.35
T
GERP RS
1.6
Varity_R
0.051
gMVP
0.017

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-27850261; API