NM_032965.6:c.316A>C

Variant names:

• chr17-35997793-T-G
• rs1285897220
• NM_032965.6:c.316A>C

Variant summary

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

The NM_032965.6(CCL15):​c.316A>C​(p.Lys106Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,613,812 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CCL15 NM_032965.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.16
• Publications: 0 publications found

Genes affected

CCL15 (HGNC:10613): (C-C motif chemokine ligand 15) This gene is located in a cluster of similar genes in the same region of chromosome 17. These genes encode CC cytokines, which are secreted proteins characterized by two adjacent cysteines. The product of this gene is chemotactic for T cells and monocytes, and acts through C-C chemokine receptor type 1 (CCR1). The proprotein is further processed into numerous smaller functional peptides. Naturally-occurring readthrough transcripts occur from this gene into the downstream gene, CCL14 (chemokine (C-C motif) ligand 14). [provided by RefSeq, Jan 2013]

CCL15-CCL14 (HGNC:44436): (CCL15-CCL14 readthrough (NMD candidate)) A cluster of CC chemokine genes exists on chromosome 17q11.2. The CC chemokines are secreted proteins characterized by two adjacent cysteines. The genes chemokine (C-C motif) ligand 14 and chemokine (C-C motif) ligand 15 are adjacent loci and express read-through transcripts spanning both loci. The read-through transcripts were originally interpreted as bicistronic transcripts, but they are represented as non-coding because they are candidates for nonsense-mediated mRNA decay (NMD). [provided by RefSeq, Dec 2009]

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=0.09332231).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032965.6. 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
	CCL15	NM_032965.6	MANE Select	c.316A>C	p.Lys106Gln	missense	Exon 4 of 4	NP_116741.2	Q16663
	CCL15-CCL14	NR_027921.3		n.862A>C		non_coding_transcript_exon	Exon 4 of 8
	CCL15-CCL14	NR_027922.3		n.862A>C		non_coding_transcript_exon	Exon 4 of 7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCL15	ENST00000617897.2	TSL:1 MANE Select	c.316A>C	p.Lys106Gln	missense	Exon 4 of 4	ENSP00000484078.1	Q16663
	CCL15-CCL14	ENST00000616694.1	TSL:2	n.316A>C		non_coding_transcript_exon	Exon 4 of 7	ENSP00000481402.1
	CCL15	ENST00000614368.1	TSL:3	c.157A>C	p.Lys53Gln	missense	Exon 2 of 3	ENSP00000484262.1	A0A087X1J9

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152206 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

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: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461606 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727134

African (AFR) AF: 0.0000299 AC: 1 AN: 33476

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

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111774

Other (OTH) AF: 0.00 AC: 0 AN: 60378

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152206 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74354

African (AFR) AF: 0.0000241 AC: 1 AN: 41454

American (AMR) AF: 0.00 AC: 0 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000988 Hom.: 0

Bravo AF: 0.0000340

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	0.43
DANN	Benign	0.42
Eigen	Benign	-0.91
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.038	N
LIST_S2	Benign	0.17	T
M_CAP	Benign	0.0014	T
MetaRNN	Benign	0.093	T
MetaSVM	Benign	-1.0	T
PhyloP100		-1.2
PrimateAI	Benign	0.24	T
Sift4G	Benign	0.52	T
Vest4		0.14
MVP		0.38
ClinPred		0.057	T
GERP RS		-1.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.12

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: rs1285897220; hg19: chr17-34324829;