17-35986613-G-A

Variant names:

• chr17-35986613-G-A
• rs760105291
• NM_032963.4:c.37C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032963.4(CCL14):​c.37C>T​(p.Leu13Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,720 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign 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: 0.0000014 (0 hom.)
• Consequence: CCL14 NM_032963.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.576

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]

ENSG00000275431 (HGNC:):

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11877796).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCL14	NM_032963.4	c.37C>T	p.Leu13Phe	missense_variant	Exon 1 of 3	ENST00000618404.5	NP_116739.1
CCL14	NM_032962.5	c.37C>T	p.Leu13Phe	missense_variant	Exon 1 of 4		NP_116738.1
CCL15-CCL14	NR_027921.3	n.1026C>T		non_coding_transcript_exon_variant	Exon 5 of 8
CCL15-CCL14	NR_027922.3	n.1026C>T		non_coding_transcript_exon_variant	Exon 5 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCL14	ENST00000618404.5	c.37C>T	p.Leu13Phe	missense_variant	Exon 1 of 3	1	NM_032963.4	ENSP00000481023.1
CCL15-CCL14	ENST00000616694.1	n.*138C>T		non_coding_transcript_exon_variant	Exon 5 of 7	2		ENSP00000481402.1
CCL15-CCL14	ENST00000616694.1	n.*138C>T		3_prime_UTR_variant	Exon 5 of 7	2		ENSP00000481402.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000803 AC: 2 AN: 248922 Hom.: 0 AF XY: 0.0000148 AC XY: 2 AN XY: 134742

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000180

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461720 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 727160

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: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000312 Hom.: 0

ExAC AF: 0.00000824 AC: 1

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 26, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.37C>T (p.L13F) alteration is located in exon 1 (coding exon 1) of the CCL14 gene. This alteration results from a C to T substitution at nucleotide position 37, causing the leucine (L) at amino acid position 13 to be replaced by a phenylalanine (F). 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	Benign	0.082
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	0.65
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T;.;.
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.095	N
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.12	T;T;T
MetaSVM	Benign	-0.95	T
PrimateAI	Benign	0.29	T
Sift4G	Uncertain	0.0060	D;D;D
Polyphen		0.12	B;B;.
Vest4		0.081
MutPred		0.56		Loss of catalytic residue at L13 (P = 0.0929);Loss of catalytic residue at L13 (P = 0.0929);Loss of catalytic residue at L13 (P = 0.0929);
MVP		0.076
ClinPred		0.076	T
GERP RS		0.27
Varity_R		0.064
gMVP		0.20

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

LitVar

Other links and lift over

dbSNP: rs760105291; hg19: chr17-34313649;