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GeneBe

17-36013769-T-C

Variant summary

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

The NM_005064.6(CCL23):c.277A>G(p.Ser93Gly) 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. 12/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

CCL23
NM_005064.6 missense

Scores

13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.636
Variant links:
Genes affected
CCL23 (HGNC:10622): (C-C motif chemokine ligand 23) This gene is one of several chemokine genes clustered on the q-arm of chromosome 17. Chemokines form a superfamily of secreted proteins involved in immunoregulatory and inflammatory processes. The superfamily is divided into four subfamilies based on the arrangement of the N-terminal cysteine residues of the mature peptide. This chemokine, a member of the CC subfamily, displays chemotactic activity on resting T lymphocytes and monocytes, lower activity on neutrophils and no activity on activated T lymphocytes. The protein is also a strong suppressor of colony formation by a multipotential hematopoietic progenitor cell line. In addition, the product of this gene is a potent agonist of the chemokine (C-C motif) receptor 1. Alternative splicing results in multiple transcript variants that encode different isoforms. [provided by RefSeq, Jul 2013]

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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=0.08511141).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CCL23NM_005064.6 linkuse as main transcriptc.277A>G p.Ser93Gly missense_variant 3/4 ENST00000615050.2
CCL23NM_145898.4 linkuse as main transcriptc.226A>G p.Ser76Gly missense_variant 3/4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CCL23ENST00000615050.2 linkuse as main transcriptc.277A>G p.Ser93Gly missense_variant 3/41 NM_005064.6 P2P55773-2
CCL23ENST00000612516.4 linkuse as main transcriptc.226A>G p.Ser76Gly missense_variant 3/41 A2P55773-1
CCL23ENST00000613876.1 linkuse as main transcriptc.13A>G p.Ser5Gly missense_variant, NMD_transcript_variant 1/23

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
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
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJul 14, 2021The c.277A>G (p.S93G) alteration is located in exon 3 (coding exon 3) of the CCL23 gene. This alteration results from a A to G substitution at nucleotide position 277, causing the serine (S) at amino acid position 93 to be replaced by a glycine (G). 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
0.096
BayesDel_addAF
Benign
-0.21
T
BayesDel_noAF
Benign
-0.54
Cadd
Benign
12
Dann
Benign
0.52
Eigen
Benign
-0.96
Eigen_PC
Benign
-0.99
FATHMM_MKL
Benign
0.033
N
M_CAP
Benign
0.0027
T
MetaRNN
Benign
0.085
T;T
MetaSVM
Benign
-0.93
T
MutationTaster
Benign
1.0
N;N
PrimateAI
Benign
0.29
T
Sift4G
Benign
0.28
T;T
Vest4
0.094
MutPred
0.54
Loss of catalytic residue at S76 (P = 0.0572);.;
MVP
0.16
ClinPred
0.14
T
GERP RS
2.6
gMVP
0.13

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: chr17-34340809; API