19-407347-C-A

Variant summary

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

The NM_001136263.2(C2CD4C):​c.1015G>T​(p.Ala339Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000717 in 1,394,568 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

C2CD4C
NM_001136263.2 missense

Scores

1
3
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.421
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=0.13667482).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
C2CD4CNM_001136263.2 linkc.1015G>T p.Ala339Ser missense_variant Exon 2 of 2 ENST00000332235.8 NP_001129735.1 Q8TF44
C2CD4CXM_011527694.2 linkc.1015G>T p.Ala339Ser 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.1015G>T p.Ala339Ser missense_variant Exon 2 of 2 2 NM_001136263.2 ENSP00000328677.4 Q8TF44

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
7.17e-7
AC:
1
AN:
1394568
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
687928
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Feb 07, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1015G>T (p.A339S) alteration is located in exon 2 (coding exon 1) of the C2CD4C gene. This alteration results from a G to T substitution at nucleotide position 1015, causing the alanine (A) at amino acid position 339 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
0.088
BayesDel_addAF
Benign
-0.12
T
BayesDel_noAF
Benign
-0.41
CADD
Benign
12
DANN
Uncertain
0.98
DEOGEN2
Benign
0.030
T
Eigen
Benign
-0.65
Eigen_PC
Benign
-0.56
FATHMM_MKL
Benign
0.33
N
LIST_S2
Uncertain
0.87
D
M_CAP
Pathogenic
0.67
D
MetaRNN
Benign
0.14
T
MetaSVM
Benign
-0.93
T
MutationAssessor
Benign
0.77
N
PrimateAI
Uncertain
0.79
T
PROVEAN
Benign
-0.56
N
REVEL
Benign
0.086
Sift
Benign
0.46
T
Sift4G
Benign
0.17
T
Polyphen
0.065
B
Vest4
0.13
MutPred
0.33
Gain of solvent accessibility (P = 0.3089);
MVP
0.12
ClinPred
0.14
T
GERP RS
2.7
Varity_R
0.046
gMVP
0.28

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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: rs1289061268; hg19: chr19-407347; API