16-57415781-G-A

Variant summary

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

The NM_002987.3(CCL17):​c.205G>A​(p.Gly69Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000521 in 1,611,816 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00035 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

CCL17
NM_002987.3 missense

Scores

1
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.13
Variant links:
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]

Genome browser will be placed here

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=0.071935624).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CCL17NM_002987.3 linkuse as main transcriptc.205G>A p.Gly69Ser missense_variant 4/4 ENST00000219244.9 NP_002978.1 Q92583
CCL17XM_017023530.2 linkuse as main transcriptc.292G>A p.Gly98Ser missense_variant 6/6 XP_016879019.1
CCL17XM_011523256.3 linkuse as main transcriptc.289G>A p.Gly97Ser missense_variant 6/6 XP_011521558.1
CCL17XM_047434448.1 linkuse as main transcriptc.205G>A p.Gly69Ser missense_variant 3/3 XP_047290404.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CCL17ENST00000219244.9 linkuse as main transcriptc.205G>A p.Gly69Ser missense_variant 4/41 NM_002987.3 ENSP00000219244.4 Q92583
CCL17ENST00000616880.1 linkuse as main transcriptc.205G>A p.Gly69Ser missense_variant 3/31 ENSP00000480147.1 Q92583

Frequencies

GnomAD3 genomes
AF:
0.000342
AC:
52
AN:
152174
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000121
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00301
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:
0.00
Gnomad OTH
AF:
0.000479
GnomAD3 exomes
AF:
0.0000398
AC:
10
AN:
251158
Hom.:
0
AF XY:
0.0000295
AC XY:
4
AN XY:
135756
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.000174
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:
0.00000881
Gnomad OTH exome
AF:
0.000326
GnomAD4 exome
AF:
0.0000212
AC:
31
AN:
1459524
Hom.:
0
Cov.:
29
AF XY:
0.0000124
AC XY:
9
AN XY:
726310
show subpopulations
Gnomad4 AFR exome
AF:
0.0000598
Gnomad4 AMR exome
AF:
0.000335
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:
0.00
Gnomad4 OTH exome
AF:
0.000232
GnomAD4 genome
AF:
0.000348
AC:
53
AN:
152292
Hom.:
0
Cov.:
32
AF XY:
0.000309
AC XY:
23
AN XY:
74454
show subpopulations
Gnomad4 AFR
AF:
0.000120
Gnomad4 AMR
AF:
0.00307
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.000474
Alfa
AF:
0.000141
Hom.:
0
Bravo
AF:
0.000752
ExAC
AF:
0.0000165
AC:
2

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 GeneticsOct 06, 2021The c.205G>A (p.G69S) alteration is located in exon 4 (coding exon 3) of the CCL17 gene. This alteration results from a G to A substitution at nucleotide position 205, causing the glycine (G) at amino acid position 69 to be replaced by a serine (S). 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
0.19
BayesDel_addAF
Benign
-0.40
T
BayesDel_noAF
Benign
-0.58
CADD
Benign
16
DANN
Benign
0.96
DEOGEN2
Benign
0.30
T;T
Eigen
Benign
-0.85
Eigen_PC
Benign
-1.0
FATHMM_MKL
Benign
0.040
N
LIST_S2
Benign
0.45
.;T
M_CAP
Benign
0.010
T
MetaRNN
Benign
0.072
T;T
MetaSVM
Benign
-0.98
T
PrimateAI
Benign
0.32
T
PROVEAN
Uncertain
-3.5
D;.
REVEL
Benign
0.076
Sift
Benign
0.060
T;.
Sift4G
Benign
0.15
T;T
Polyphen
0.81
P;P
Vest4
0.22
MutPred
0.63
Gain of disorder (P = 0.093);Gain of disorder (P = 0.093);
MVP
0.14
MPC
0.90
ClinPred
0.15
T
GERP RS
0.93
Varity_R
0.44
gMVP
0.48

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs570762119; hg19: chr16-57449693; COSMIC: COSV54664532; API