5-205323-C-G

Variant summary

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

The NM_145265.3(CCDC127):​c.757G>C​(p.Val253Leu) 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. 16/21 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)

Consequence

CCDC127
NM_145265.3 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.58
Variant links:
Genes affected
CCDC127 (HGNC:30520): (coiled-coil domain containing 127) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

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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=0.12768209).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CCDC127NM_145265.3 linkc.757G>C p.Val253Leu missense_variant Exon 3 of 3 ENST00000296824.4 NP_660308.1 Q96BQ5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CCDC127ENST00000296824.4 linkc.757G>C p.Val253Leu missense_variant Exon 3 of 3 1 NM_145265.3 ENSP00000296824.2 Q96BQ5

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

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

The c.757G>C (p.V253L) alteration is located in exon 3 (coding exon 2) of the CCDC127 gene. This alteration results from a G to C substitution at nucleotide position 757, causing the valine (V) at amino acid position 253 to be replaced by a leucine (L). 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
0.24
BayesDel_addAF
Benign
-0.037
T
BayesDel_noAF
Benign
-0.29
CADD
Benign
14
DANN
Benign
0.77
DEOGEN2
Benign
0.023
T
Eigen
Benign
-0.67
Eigen_PC
Benign
-0.64
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Benign
0.77
T
M_CAP
Benign
0.041
D
MetaRNN
Benign
0.13
T
MetaSVM
Benign
-0.41
T
MutationAssessor
Benign
1.9
L
PrimateAI
Benign
0.31
T
PROVEAN
Benign
-0.98
N
REVEL
Benign
0.26
Sift
Benign
0.14
T
Sift4G
Benign
0.14
T
Polyphen
0.0030
B
Vest4
0.10
MutPred
0.29
Loss of methylation at K248 (P = 0.1008);
MVP
0.43
MPC
0.19
ClinPred
0.080
T
GERP RS
2.7
Varity_R
0.060
gMVP
0.72

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
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: rs1734148809; hg19: chr5-205438; API