17-35977661-C-A

Variant names:

• chr17-35977661-C-A
• rs1383472032
• NM_004590.4:c.268G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004590.4(CCL16):​c.268G>T​(p.Asp90Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,078 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D90N) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CCL16 NM_004590.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.102
• Publications: 0 publications found

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]

ENSG00000270240 (HGNC:58767):

ENSG00000302706 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.119897276).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004590.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCL16	NM_004590.4	MANE Select	c.268G>T	p.Asp90Tyr	missense	Exon 3 of 3	NP_004581.1	O15467

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCL16	ENST00000611905.2	TSL:1 MANE Select	c.268G>T	p.Asp90Tyr	missense	Exon 3 of 3	ENSP00000478024.1	O15467
	CCL16	ENST00000890729.1		c.289G>T	p.Asp97Tyr	missense	Exon 3 of 3	ENSP00000560788.1
	CCL16	ENST00000890728.1		c.265G>T	p.Asp89Tyr	missense	Exon 3 of 3	ENSP00000560787.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460078 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726336

African (AFR) AF: 0.00 AC: 0 AN: 33424

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86174

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4282

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111996

Other (OTH) AF: 0.00 AC: 0 AN: 60226

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.052	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	14
DANN	Uncertain	0.98
DEOGEN2	Benign	0.024	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.6	L
PhyloP100		-0.10
PrimateAI	Benign	0.35	T
Sift4G	Uncertain	0.011	D
Polyphen		0.28	B
Vest4		0.37
MutPred		0.50		Loss of ubiquitination at K89 (P = 0.0596)
MVP		0.31
ClinPred		0.81	D
GERP RS		-0.55
Varity_R		0.20
gMVP		0.59

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

Other links and lift over

dbSNP: rs1383472032; hg19: chr17-34304697;