16-57415102-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.92G>A​(p.Arg31Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000415 in 1,613,536 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 0.000039 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000042 ( 0 hom. )

Consequence

CCL17
NM_002987.3 missense

Scores

1
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.189
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=0.109387994).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CCL17NM_002987.3 linkuse as main transcriptc.92G>A p.Arg31Gln missense_variant 3/4 ENST00000219244.9 NP_002978.1 Q92583
CCL17XM_017023530.2 linkuse as main transcriptc.179G>A p.Arg60Gln missense_variant 5/6 XP_016879019.1
CCL17XM_011523256.3 linkuse as main transcriptc.176G>A p.Arg59Gln missense_variant 5/6 XP_011521558.1
CCL17XM_047434448.1 linkuse as main transcriptc.92G>A p.Arg31Gln missense_variant 2/3 XP_047290404.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CCL17ENST00000219244.9 linkuse as main transcriptc.92G>A p.Arg31Gln missense_variant 3/41 NM_002987.3 ENSP00000219244.4 Q92583
CCL17ENST00000616880.1 linkuse as main transcriptc.92G>A p.Arg31Gln missense_variant 2/31 ENSP00000480147.1 Q92583

Frequencies

GnomAD3 genomes
AF:
0.0000394
AC:
6
AN:
152156
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.0000942
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000588
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.0000517
AC:
13
AN:
251388
Hom.:
0
AF XY:
0.0000515
AC XY:
7
AN XY:
135882
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.0000925
Gnomad NFE exome
AF:
0.0000879
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000417
AC:
61
AN:
1461380
Hom.:
0
Cov.:
31
AF XY:
0.0000481
AC XY:
35
AN XY:
727060
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000348
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.0000477
Gnomad4 OTH exome
AF:
0.0000662
GnomAD4 genome
AF:
0.0000394
AC:
6
AN:
152156
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74326
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0000942
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.000478
Alfa
AF:
0.0000565
Hom.:
0
Bravo
AF:
0.0000378
ExAC
AF:
0.0000412
AC:
5
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.0000545
EpiControl
AF:
0.0000593

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 GeneticsMay 18, 2022The c.92G>A (p.R31Q) 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 92, causing the arginine (R) at amino acid position 31 to be replaced by a glutamine (Q). 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
0.13
BayesDel_addAF
Benign
-0.40
T
BayesDel_noAF
Benign
-0.62
CADD
Benign
17
DANN
Uncertain
1.0
DEOGEN2
Benign
0.15
T;T
Eigen
Benign
-0.16
Eigen_PC
Benign
-0.13
FATHMM_MKL
Benign
0.11
N
LIST_S2
Benign
0.75
.;T
M_CAP
Benign
0.019
T
MetaRNN
Benign
0.11
T;T
MetaSVM
Benign
-1.0
T
PrimateAI
Benign
0.29
T
PROVEAN
Benign
-1.8
N;.
REVEL
Benign
0.070
Sift
Benign
0.17
T;.
Sift4G
Benign
0.065
T;T
Polyphen
0.69
P;P
Vest4
0.24
MutPred
0.47
Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);
MVP
0.19
MPC
0.56
ClinPred
0.20
T
GERP RS
3.9
Varity_R
0.42
gMVP
0.30

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: rs377361646; hg19: chr16-57449014; COSMIC: COSV54664821; API