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GeneBe

17-36013820-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_005064.6(CCL23):c.226A>G(p.Thr76Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000176 in 1,613,946 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.000079 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00019 ( 0 hom. )

Consequence

CCL23
NM_005064.6 missense

Scores

13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.86
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.06285381).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CCL23NM_005064.6 linkuse as main transcriptc.226A>G p.Thr76Ala missense_variant 3/4 ENST00000615050.2
CCL23NM_145898.4 linkuse as main transcriptc.175A>G p.Thr59Ala missense_variant 3/4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CCL23ENST00000615050.2 linkuse as main transcriptc.226A>G p.Thr76Ala missense_variant 3/41 NM_005064.6 P2P55773-2
CCL23ENST00000612516.4 linkuse as main transcriptc.175A>G p.Thr59Ala missense_variant 3/41 A2P55773-1
CCL23ENST00000613876.1 linkuse as main transcript upstream_gene_variant 3

Frequencies

GnomAD3 genomes
AF:
0.0000789
AC:
12
AN:
152100
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000557
AC:
14
AN:
251458
Hom.:
0
AF XY:
0.0000589
AC XY:
8
AN XY:
135904
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
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:
0.000105
Gnomad OTH exome
AF:
0.000326
GnomAD4 exome
AF:
0.000186
AC:
272
AN:
1461846
Hom.:
0
Cov.:
32
AF XY:
0.000186
AC XY:
135
AN XY:
727228
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
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:
0.000234
Gnomad4 OTH exome
AF:
0.000199
GnomAD4 genome
AF:
0.0000789
AC:
12
AN:
152100
Hom.:
0
Cov.:
32
AF XY:
0.0000538
AC XY:
4
AN XY:
74300
show subpopulations
Gnomad4 AFR
AF:
0.0000483
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000152
Hom.:
0
Bravo
AF:
0.0000416
TwinsUK
AF:
0.000539
AC:
2
ALSPAC
AF:
0.000519
AC:
2
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000659
AC:
8
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.000109
EpiControl
AF:
0.000119

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 GeneticsJun 24, 2022The c.226A>G (p.T76A) 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 226, causing the threonine (T) at amino acid position 76 to be replaced by an alanine (A). 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
0.16
BayesDel_addAF
Benign
-0.49
T
BayesDel_noAF
Benign
-0.73
Cadd
Benign
1.0
Dann
Benign
0.77
Eigen
Benign
-1.0
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.0098
N
M_CAP
Benign
0.0022
T
MetaRNN
Benign
0.063
T;T
MetaSVM
Benign
-0.99
T
MutationTaster
Benign
1.0
N;N
PrimateAI
Benign
0.23
T
Sift4G
Benign
0.32
T;T
Vest4
0.052
MVP
0.27
ClinPred
0.058
T
GERP RS
-1.2
gMVP
0.22

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs199911286; hg19: chr17-34340860; API