19-407475-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001136263.2(C2CD4C):​c.887G>C​(p.Arg296Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000137 in 1,383,234 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

C2CD4C
NM_001136263.2 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.46
Variant links:
Genes affected
C2CD4C (HGNC:29417): (C2 calcium dependent domain containing 4C) Predicted to be active in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.11474645).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
C2CD4CNM_001136263.2 linkc.887G>C p.Arg296Pro missense_variant Exon 2 of 2 ENST00000332235.8 NP_001129735.1 Q8TF44
C2CD4CXM_011527694.2 linkc.887G>C p.Arg296Pro missense_variant Exon 2 of 3 XP_011525996.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
C2CD4CENST00000332235.8 linkc.887G>C p.Arg296Pro missense_variant Exon 2 of 2 2 NM_001136263.2 ENSP00000328677.4 Q8TF44

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
151982
Hom.:
0
Cov.:
33
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.0000146
AC:
18
AN:
1231252
Hom.:
0
Cov.:
31
AF XY:
0.00000839
AC XY:
5
AN XY:
596096
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:
0.0000169
Gnomad4 OTH exome
AF:
0.0000198
GnomAD4 genome
AF:
0.00000658
AC:
1
AN:
151982
Hom.:
0
Cov.:
33
AF XY:
0.0000135
AC XY:
1
AN XY:
74248
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:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000264

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Nov 10, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.887G>C (p.R296P) alteration is located in exon 2 (coding exon 1) of the C2CD4C gene. This alteration results from a G to C substitution at nucleotide position 887, causing the arginine (R) at amino acid position 296 to be replaced by a proline (P). 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
0.080
BayesDel_addAF
Benign
-0.31
T
BayesDel_noAF
Benign
-0.68
CADD
Benign
15
DANN
Benign
0.75
DEOGEN2
Benign
0.014
T
Eigen
Benign
-0.72
Eigen_PC
Benign
-0.71
FATHMM_MKL
Benign
0.32
N
LIST_S2
Benign
0.34
T
M_CAP
Benign
0.0080
T
MetaRNN
Benign
0.11
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.76
N
PrimateAI
Pathogenic
0.91
D
PROVEAN
Benign
-1.1
N
REVEL
Benign
0.045
Sift
Benign
0.10
T
Sift4G
Benign
0.22
T
Polyphen
0.0010
B
Vest4
0.21
MVP
0.14
ClinPred
0.10
T
GERP RS
2.8
Varity_R
0.16
gMVP
0.46

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: rs950944713; hg19: chr19-407475; API