rs375335603

Variant names:

• chr17-35984356-C-A
• NM_032963.4:c.176G>T

Your query was ambiguous. Multiple possible variants found:

• chr17-35984356-C-A
• chr17-35984356-C-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_032963.4(CCL14):​c.176G>T​(p.Cys59Phe) 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 1,460,898 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CCL14 NM_032963.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.87

Genes affected

CCL14 (HGNC:10612): (C-C motif chemokine ligand 14) This gene, chemokine (C-C motif) ligand 14, is one of several CC cytokine genes clustered on 17q11.2. The CC cytokines are secreted proteins characterized by two adjacent cysteines. The cytokine encoded by this gene induces changes in intracellular calcium concentration and enzyme release in monocytes. Multiple transcript variants encoding different isoforms have been found for this gene. Read-through transcripts are also expressed that include exons from the upstream cytokine gene, chemokine (C-C motif) ligand 15, and are represented as GeneID: 348249. [provided by RefSeq, Dec 2009]

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]

ENSG00000275431 (HGNC:):

ACMG classification

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, 0.973

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCL14	NM_032963.4	c.176G>T	p.Cys59Phe	missense_variant	Exon 2 of 3	ENST00000618404.5	NP_116739.1
CCL14	NM_032962.5	c.224G>T	p.Cys75Phe	missense_variant	Exon 3 of 4		NP_116738.1
CCL15-CCL14	NR_027921.3	n.1213G>T		non_coding_transcript_exon_variant	Exon 7 of 8
CCL15-CCL14	NR_027922.3	n.1165G>T		non_coding_transcript_exon_variant	Exon 6 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCL14	ENST00000618404.5	c.176G>T	p.Cys59Phe	missense_variant	Exon 2 of 3	1	NM_032963.4	ENSP00000481023.1
CCL15-CCL14	ENST00000616694.1	n.*277G>T		non_coding_transcript_exon_variant	Exon 6 of 7	2		ENSP00000481402.1
CCL15-CCL14	ENST00000616694.1	n.*277G>T		3_prime_UTR_variant	Exon 6 of 7	2		ENSP00000481402.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460898 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726836

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: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.88
BayesDel_addAF	Pathogenic	0.41	D
BayesDel_noAF	Pathogenic	0.35
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.50	D;T;.;.
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Uncertain	0.79	D
M_CAP	Benign	0.051	D
MetaRNN	Pathogenic	0.97	D;D;D;D
MetaSVM	Uncertain	0.64	D
PrimateAI	Uncertain	0.53	T
Sift4G	Uncertain	0.0020	D;D;D;D
Polyphen		1.0	.;D;D;.
Vest4		0.66
MutPred		0.99		.;Gain of ubiquitination at K61 (P = 0.1062);.;Gain of ubiquitination at K61 (P = 0.1062);
MVP		0.23
ClinPred		0.95	D
GERP RS		5.1
Varity_R		0.80
gMVP		0.77

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr17-34311392;