Variant 16-57415192-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_002987.3(CCL17):c.182C>T(p.Ala61Val) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CCL17
NM_002987.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.36

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]

CCL17 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.965

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CCL17	NM_002987.3 linkuse as main transcript	c.182C>T	p.Ala61Val	missense_variant	3/4	ENST00000219244.9
CCL17	XM_017023530.2 linkuse as main transcript	c.269C>T	p.Ala90Val	missense_variant	5/6
CCL17	XM_011523256.3 linkuse as main transcript	c.266C>T	p.Ala89Val	missense_variant	5/6
CCL17	XM_047434448.1 linkuse as main transcript	c.182C>T	p.Ala61Val	missense_variant	2/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCL17	ENST00000219244.9 linkuse as main transcript	c.182C>T	p.Ala61Val	missense_variant	3/4	1	NM_002987.3	P1
CCL17	ENST00000616880.1 linkuse as main transcript	c.182C>T	p.Ala61Val	missense_variant	2/3	1		P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1448760

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

721656

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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 submitter

clinical testing

Ambry Genetics

Mar 28, 2024

The c.182C>T (p.A61V) alteration is located in exon 3 (coding exon 2) of the CCL17 gene. This alteration results from a C to T substitution at nucleotide position 182, causing the alanine (A) at amino acid position 61 to be replaced by a valine (V). 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

0.88

BayesDel_addAF

Pathogenic

0.17

BayesDel_noAF

Uncertain

0.0

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.38

T;T

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.71

.;T

M_CAP

Benign

0.053

MetaRNN

Pathogenic

0.96

D;D

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

PrimateAI

Benign

0.39

PROVEAN

Uncertain

-3.7

D;.

REVEL

Uncertain

0.37

Sift

Uncertain

0.0060

D;.

Sift4G

Uncertain

0.0080

D;D

Polyphen

1.0

D;D

Vest4

0.58

MutPred

0.84

Loss of catalytic residue at A61 (P = 0.0494);Loss of catalytic residue at A61 (P = 0.0494);

MVP

0.36

MPC

0.97

ClinPred

0.98

GERP RS

5.1

Varity_R

0.83

gMVP

0.85

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over