chr16-57415131-G-A

Position:

• chr16-57415131-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002987.3(CCL17):​c.121G>A​(p.Ala41Thr) 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. 12/20 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: CCL17 NM_002987.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.100

Genes affected

CCL17 (HGNC:10615): (C-C motif chemokine ligand 17) This antimicrobial gene is one of several Cys-Cys (CC) cytokine genes clustered on the q arm of chromosome 16. Cytokines are a family of secreted proteins involved in immunoregulatory and inflammatory processes. The CC cytokines are proteins characterized by two adjacent cysteines. The cytokine encoded by this gene displays chemotactic activity for T lymphocytes, but not monocytes or granulocytes. The product of this gene binds to chemokine receptors CCR4 and CCR8. This chemokine plays important roles in T cell development in thymus as well as in trafficking and activation of mature T cells. [provided by RefSeq, Sep 2014]

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=0.23206738).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCL17	NM_002987.3	c.121G>A	p.Ala41Thr	missense_variant	3/4	ENST00000219244.9	NP_002978.1
CCL17	XM_017023530.2	c.208G>A	p.Ala70Thr	missense_variant	5/6		XP_016879019.1
CCL17	XM_011523256.3	c.205G>A	p.Ala69Thr	missense_variant	5/6		XP_011521558.1
CCL17	XM_047434448.1	c.121G>A	p.Ala41Thr	missense_variant	2/3		XP_047290404.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCL17	ENST00000219244.9	c.121G>A	p.Ala41Thr	missense_variant	3/4	1	NM_002987.3	ENSP00000219244.4
CCL17	ENST00000616880.1	c.121G>A	p.Ala41Thr	missense_variant	2/3	1		ENSP00000480147.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Jun 29, 2023

The c.121G>A (p.A41T) alteration is located in exon 3 (coding exon 2) of the CCL17 gene. This alteration results from a G to A substitution at nucleotide position 121, causing the alanine (A) at amino acid position 41 to be replaced by a threonine (T). 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	0.11
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	15
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T;T
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.34
FATHMM_MKL	Benign	0.094	N
LIST_S2	Benign	0.75	.;T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.23	T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.28	T
PROVEAN	Uncertain	-2.4	N;.
REVEL	Benign	0.023
Sift	Benign	0.070	T;.
Sift4G	Benign	0.075	T;T
Polyphen		0.96	D;D
Vest4		0.22
MutPred		0.32		Loss of catalytic residue at A41 (P = 0.0606);Loss of catalytic residue at A41 (P = 0.0606);
MVP		0.19
MPC		0.64
ClinPred		0.75	D
GERP RS		2.9
Varity_R		0.27
gMVP		0.31

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-57449043;