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GeneBe

17-36013804-G-A

Variant summary

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

The NM_005064.6(CCL23):c.242C>T(p.Pro81Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000427 in 1,614,058 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00023 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

CCL23
NM_005064.6 missense

Scores

1
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.96
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=0.07736671).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CCL23NM_005064.6 linkuse as main transcriptc.242C>T p.Pro81Leu missense_variant 3/4 ENST00000615050.2
CCL23NM_145898.4 linkuse as main transcriptc.191C>T p.Pro64Leu missense_variant 3/4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CCL23ENST00000615050.2 linkuse as main transcriptc.242C>T p.Pro81Leu missense_variant 3/41 NM_005064.6 P2P55773-2
CCL23ENST00000612516.4 linkuse as main transcriptc.191C>T p.Pro64Leu missense_variant 3/41 A2P55773-1
CCL23ENST00000613876.1 linkuse as main transcript upstream_gene_variant 3

Frequencies

GnomAD3 genomes
AF:
0.000230
AC:
35
AN:
152186
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000820
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000517
AC:
13
AN:
251430
Hom.:
0
AF XY:
0.0000368
AC XY:
5
AN XY:
135892
show subpopulations
Gnomad AFR exome
AF:
0.000554
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000109
Gnomad SAS exome
AF:
0.0000653
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000233
AC:
34
AN:
1461872
Hom.:
0
Cov.:
32
AF XY:
0.0000151
AC XY:
11
AN XY:
727240
show subpopulations
Gnomad4 AFR exome
AF:
0.000806
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000348
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000270
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.000230
AC:
35
AN:
152186
Hom.:
0
Cov.:
32
AF XY:
0.000229
AC XY:
17
AN XY:
74352
show subpopulations
Gnomad4 AFR
AF:
0.000820
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000290
Hom.:
0
Bravo
AF:
0.000227
ESP6500AA
AF:
0.00159
AC:
7
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000824
AC:
10

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 GeneticsMar 17, 2023The c.242C>T (p.P81L) alteration is located in exon 3 (coding exon 3) of the CCL23 gene. This alteration results from a C to T substitution at nucleotide position 242, causing the proline (P) at amino acid position 81 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
Uncertain
0.47
BayesDel_addAF
Benign
-0.51
T
BayesDel_noAF
Benign
-0.57
Cadd
Benign
12
Dann
Benign
0.92
Eigen
Benign
-0.78
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.023
N
M_CAP
Benign
0.019
T
MetaRNN
Benign
0.077
T;T
MetaSVM
Benign
-1.2
T
MutationTaster
Benign
0.72
N;N
PrimateAI
Benign
0.23
T
Sift4G
Benign
0.12
T;T
Vest4
0.11
MVP
0.25
ClinPred
0.54
D
GERP RS
-7.4
gMVP
0.34

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: rs142522197; hg19: chr17-34340844; API