NM_005064.6:c.124G>T

Variant names:

• chr17-36014346-C-A
• rs1845107384
• NM_005064.6:c.124G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005064.6(CCL23):​c.124G>T​(p.Val42Leu) 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. 13/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V42I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCL23 NM_005064.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.39
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06293595).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005064.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCL23	NM_005064.6	MANE Select	c.124G>T	p.Val42Leu	missense	Exon 2 of 4	NP_005055.3
	CCL23	NM_145898.4		c.124G>T	p.Val42Leu	missense	Exon 2 of 4	NP_665905.2	P55773-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCL23	ENST00000615050.2	TSL:1 MANE Select	c.124G>T	p.Val42Leu	missense	Exon 2 of 4	ENSP00000481357.1	P55773-2
	CCL23	ENST00000612516.4	TSL:1	c.124G>T	p.Val42Leu	missense	Exon 2 of 4	ENSP00000484748.1	P55773-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000312 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.0010
DANN	Benign	0.17
Eigen	Benign	-1.9
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.0038	N
M_CAP	Benign	0.0012	T
MetaRNN	Benign	0.063	T
MetaSVM	Benign	-0.96	T
PhyloP100		-4.4
PrimateAI	Benign	0.20	T
Sift4G	Benign	0.81	T
Vest4		0.10
MutPred		0.34		Gain of loop (P = 0.1069)
MVP		0.18
ClinPred		0.14	T
GERP RS		-4.1
gMVP		0.13

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1845107384; hg19: chr17-34341386;