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GeneBe

2-130339209-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_032357.4(CCDC115):c.454G>A(p.Ala152Thr) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

CCDC115
NM_032357.4 missense

Scores

7
7
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.14
Variant links:
Genes affected
CCDC115 (HGNC:28178): (coiled-coil domain containing 115) The protein encoded by this gene has been observed to localize to the endoplasmic reticulum (ER)-Golgi intermediate compartment (ERGIC) and coat protein complex I (COPI) vesicles in some human cells. The encoded protein shares some homology with the yeast V-ATPase assembly factor Vma22p, and the orthologous protein in mouse promotes cell proliferation and suppresses cell death. Defects in this gene are a cause of congenital disorder of glycosylation, type IIo in humans. [provided by RefSeq, Mar 2016]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.832

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CCDC115NM_032357.4 linkuse as main transcriptc.454G>A p.Ala152Thr missense_variant 5/5 ENST00000259229.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CCDC115ENST00000259229.7 linkuse as main transcriptc.454G>A p.Ala152Thr missense_variant 5/51 NM_032357.4 P1Q96NT0-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
33

ClinVar

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

Submissions by phenotype

Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsNov 07, 2022The c.454G>A (p.A152T) alteration is located in exon 5 (coding exon 5) of the CCDC115 gene. This alteration results from a G to A substitution at nucleotide position 454, causing the alanine (A) at amino acid position 152 to be replaced by a threonine (T). 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
0.32
BayesDel_addAF
Pathogenic
0.24
D
BayesDel_noAF
Uncertain
0.11
Cadd
Pathogenic
26
Dann
Pathogenic
1.0
DEOGEN2
Benign
0.30
T;T
Eigen
Uncertain
0.64
Eigen_PC
Uncertain
0.57
FATHMM_MKL
Uncertain
0.90
D
LIST_S2
Benign
0.82
T;T
M_CAP
Pathogenic
0.44
D
MetaRNN
Pathogenic
0.83
D;D
MetaSVM
Pathogenic
0.95
D
MutationAssessor
Pathogenic
3.2
M;.
MutationTaster
Benign
0.90
D;D;D
PrimateAI
Uncertain
0.58
T
PROVEAN
Uncertain
-3.3
D;D
REVEL
Pathogenic
0.77
Sift
Uncertain
0.0070
D;D
Sift4G
Benign
0.071
T;D
Polyphen
1.0
D;D
Vest4
0.65
MutPred
0.56
Gain of relative solvent accessibility (P = 0.0479);.;
MVP
0.98
MPC
0.89
ClinPred
0.99
D
GERP RS
4.0
Varity_R
0.44
gMVP
0.69

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: chr2-131096782; API