16-57415129-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_002987.3(CCL17):​c.119G>A​(p.Gly40Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00026 in 1,613,966 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00028 ( 1 hom. )

Consequence

CCL17
NM_002987.3 missense

Scores

1
2
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.06
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 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.3928507).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CCL17NM_002987.3 linkuse as main transcriptc.119G>A p.Gly40Glu missense_variant 3/4 ENST00000219244.9
CCL17XM_017023530.2 linkuse as main transcriptc.206G>A p.Gly69Glu missense_variant 5/6
CCL17XM_011523256.3 linkuse as main transcriptc.203G>A p.Gly68Glu missense_variant 5/6
CCL17XM_047434448.1 linkuse as main transcriptc.119G>A p.Gly40Glu missense_variant 2/3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CCL17ENST00000219244.9 linkuse as main transcriptc.119G>A p.Gly40Glu missense_variant 3/41 NM_002987.3 P1
CCL17ENST00000616880.1 linkuse as main transcriptc.119G>A p.Gly40Glu missense_variant 2/31 P1

Frequencies

GnomAD3 genomes
AF:
0.000112
AC:
17
AN:
152166
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
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:
0.000235
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000103
AC:
26
AN:
251450
Hom.:
0
AF XY:
0.0000883
AC XY:
12
AN XY:
135908
show subpopulations
Gnomad AFR exome
AF:
0.0000615
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:
0.000211
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.000275
AC:
402
AN:
1461800
Hom.:
1
Cov.:
31
AF XY:
0.000250
AC XY:
182
AN XY:
727220
show subpopulations
Gnomad4 AFR exome
AF:
0.0000896
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:
0.000337
Gnomad4 OTH exome
AF:
0.000397
GnomAD4 genome
AF:
0.000112
AC:
17
AN:
152166
Hom.:
0
Cov.:
32
AF XY:
0.000121
AC XY:
9
AN XY:
74324
show subpopulations
Gnomad4 AFR
AF:
0.0000241
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:
0.000235
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000225
Hom.:
0
Bravo
AF:
0.000102
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000576
AC:
7
EpiCase
AF:
0.000109
EpiControl
AF:
0.000296

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 GeneticsNov 30, 2021The c.119G>A (p.G40E) 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 119, causing the glycine (G) at amino acid position 40 to be replaced by a glutamic acid (E). 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
Pathogenic
0.72
BayesDel_addAF
Benign
-0.39
T
BayesDel_noAF
Benign
-0.49
CADD
Benign
22
DANN
Uncertain
1.0
DEOGEN2
Benign
0.11
T;T
Eigen
Benign
-0.0032
Eigen_PC
Benign
-0.16
FATHMM_MKL
Benign
0.13
N
LIST_S2
Benign
0.71
.;T
M_CAP
Benign
0.014
T
MetaRNN
Benign
0.39
T;T
MetaSVM
Benign
-1.0
T
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.44
T
PROVEAN
Uncertain
-3.3
D;.
REVEL
Benign
0.085
Sift
Benign
0.13
T;.
Sift4G
Benign
0.28
T;T
Polyphen
0.98
D;D
Vest4
0.51
MVP
0.27
MPC
1.1
ClinPred
0.12
T
GERP RS
3.0
Varity_R
0.59
gMVP
0.61

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: rs372792230; hg19: chr16-57449041; API