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GeneBe

17-36013908-C-T

Variant summary

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

The NM_005064.6(CCL23):c.138G>A(p.Met46Ile) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,354 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

CCL23
NM_005064.6 missense, splice_region

Scores

12
Splicing: ADA: 0.00005263
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0170
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=0.13015172).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CCL23NM_005064.6 linkuse as main transcriptc.138G>A p.Met46Ile missense_variant, splice_region_variant 3/4 ENST00000615050.2
CCL23NM_145898.4 linkuse as main transcriptc.137-50G>A intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CCL23ENST00000615050.2 linkuse as main transcriptc.138G>A p.Met46Ile missense_variant, splice_region_variant 3/41 NM_005064.6 P2P55773-2
CCL23ENST00000612516.4 linkuse as main transcriptc.137-50G>A intron_variant 1 A2P55773-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000119
AC:
3
AN:
251102
Hom.:
0
AF XY:
0.00000737
AC XY:
1
AN XY:
135696
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000868
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000274
AC:
4
AN:
1461354
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
727010
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000671
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:
9.00e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000756

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 27, 2022The c.138G>A (p.M46I) alteration is located in exon 3 (coding exon 3) of the CCL23 gene. This alteration results from a G to A substitution at nucleotide position 138, causing the methionine (M) at amino acid position 46 to be replaced by an isoleucine (I). 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
BayesDel_addAF
Benign
-0.43
T
BayesDel_noAF
Benign
-0.65
Cadd
Benign
3.1
Dann
Benign
0.64
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.4
FATHMM_MKL
Benign
0.00032
N
M_CAP
Benign
0.0024
T
MetaRNN
Benign
0.13
T
MetaSVM
Benign
-0.91
T
MutationTaster
Benign
1.0
N;N
PrimateAI
Benign
0.21
T
Sift4G
Benign
0.45
T
Vest4
0.076
MutPred
0.48
Loss of catalytic residue at V42 (P = 0.1358);
MVP
0.25
ClinPred
0.048
T
GERP RS
-6.6
gMVP
0.20

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.000053
dbscSNV1_RF
Benign
0.0020
SpliceAI score (max)
0.060
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: rs947326166; hg19: chr17-34340948; API