17-36013769-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.636

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]

ACMG classification

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
CCL23	NM_005064.6	c.277A>G	p.Ser93Gly	missense_variant	3/4	ENST00000615050.2
CCL23	NM_145898.4	c.226A>G	p.Ser76Gly	missense_variant	3/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCL23	ENST00000615050.2	c.277A>G	p.Ser93Gly	missense_variant	3/4	1	NM_005064.6	P2
CCL23	ENST00000612516.4	c.226A>G	p.Ser76Gly	missense_variant	3/4	1		A2
CCL23	ENST00000613876.1	c.13A>G	p.Ser5Gly	missense_variant, NMD_transcript_variant	1/2	3

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

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 14, 2021

The 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;