chr17-35977720-T-A

Variant names:

• chr17-35977720-T-A
• NM_004590.4:c.209A>T

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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.587

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]

ACMG classification

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 rank	MANE	Protein	UniProt
CCL16	NM_004590.4	c.209A>T	p.Lys70Met	missense_variant	Exon 3 of 3	ENST00000611905.2	NP_004581.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCL16	ENST00000611905.2	c.209A>T	p.Lys70Met	missense_variant	Exon 3 of 3	1	NM_004590.4	ENSP00000478024.1
CCL16	ENST00000610493.1	n.*279A>T		non_coding_transcript_exon_variant	Exon 5 of 5	5		ENSP00000478934.1
CCL16	ENST00000613642.4	n.131A>T		non_coding_transcript_exon_variant	Exon 2 of 3	3		ENSP00000478592.1
CCL16	ENST00000610493.1	n.*279A>T		3_prime_UTR_variant	Exon 5 of 5	5		ENSP00000478934.1

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

Submissions by phenotype

not specified Uncertain:1

Aug 04, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The 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
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;