17-35977720-T-A

Variant summary

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

The NM_004590.4(CCL16):​c.209A>T​(p.Lys70Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

CCL16
NM_004590.4 missense

Scores

1
6
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.587
Variant links:
Genes affected
CCL16 (HGNC:10614): (C-C motif chemokine ligand 16) This gene is one of several cytokine genes clustered on the q-arm of chromosome 17. 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 lymphocytes and monocytes but not for neutrophils. This cytokine also shows a potent myelosuppressive activity and suppresses proliferation of myeloid progenitor cells. The expression of this gene is upregulated by IL-10. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CCL16NM_004590.4 linkuse as main transcriptc.209A>T p.Lys70Met missense_variant 3/3 ENST00000611905.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CCL16ENST00000611905.2 linkuse as main transcriptc.209A>T p.Lys70Met missense_variant 3/31 NM_004590.4 P1
CCL16ENST00000613642.4 linkuse as main transcriptc.134A>T p.Lys45Met missense_variant, NMD_transcript_variant 2/33
CCL16ENST00000610493.1 linkuse as main transcriptc.*279A>T 3_prime_UTR_variant, NMD_transcript_variant 5/55

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
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsAug 04, 2023The c.209A>T (p.K70M) alteration is located in exon 3 (coding exon 3) of the CCL16 gene. This alteration results from a A to T substitution at nucleotide position 209, causing the lysine (K) at amino acid position 70 to be replaced by a methionine (M). 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
Uncertain
0.55
BayesDel_addAF
Uncertain
0.031
T
BayesDel_noAF
Benign
-0.19
CADD
Benign
21
DANN
Uncertain
0.99
DEOGEN2
Benign
0.067
T
Eigen
Uncertain
0.26
Eigen_PC
Benign
0.046
FATHMM_MKL
Benign
0.59
D
LIST_S2
Benign
0.66
T
M_CAP
Benign
0.0040
T
MetaRNN
Uncertain
0.62
D
MetaSVM
Benign
-1.0
T
MutationAssessor
Pathogenic
3.8
H
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.40
T
Sift4G
Uncertain
0.016
D
Polyphen
1.0
D
Vest4
0.32
MutPred
0.69
Loss of methylation at K70 (P = 0.0095);
MVP
0.65
ClinPred
0.89
D
GERP RS
-1.8
Varity_R
0.29
gMVP
0.72

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-34304756; API