16-57379667-C-A

Variant names:

• chr16-57379667-C-A
• NM_002996.6:c.104C>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_002996.6(CX3CL1):​c.104C>A​(p.Thr35Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 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: 33)
• Consequence: CX3CL1 NM_002996.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.69

Genes affected

CX3CL1 (HGNC:10647): (C-X3-C motif chemokine ligand 1) This gene belongs to the CX3C subgroup of chemokines, characterized by the number of amino acids located between the conserved cysteine residues. This is the only member of the CX3C subgroup, which contains three amino acids between cysteine residues, resulting in a Cys-X-X-X-Cys configuration. The encoded protein contains an extended mucin-like stalk with a chemokine domain on top, and exists in both a membrane-anchored form where it acts as a binding molecule, or, in soluble form, as a chemotactic cytokine. The mature form of this protein can be cleaved at the cell surface, yielding different soluble forms that can interact with the G-protein coupled receptor, C-X3-C motif chemokine receptor 1 gene product. This gene plays a role in a wide range of diseases, including cancer, vasculitis, neuropathies, atherosclerosis, inflammatory diseases, and in human immunodeficiency virus infections. [provided by RefSeq, Sep 2017]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3599115).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CX3CL1	NM_002996.6	c.104C>A	p.Thr35Lys	missense_variant	Exon 2 of 3	ENST00000006053.7	NP_002987.1
CX3CL1	NM_001304392.3	c.-64-2363C>A		intron_variant	Intron 1 of 1		NP_001291321.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CX3CL1	ENST00000006053.7	c.104C>A	p.Thr35Lys	missense_variant	Exon 2 of 3	1	NM_002996.6	ENSP00000006053.6
CX3CL1	ENST00000565912	c.-11C>A		5_prime_UTR_variant	Exon 1 of 2	1		ENSP00000464114.1
CX3CL1	ENST00000563383.1	c.122C>A	p.Thr41Lys	missense_variant	Exon 2 of 3	5		ENSP00000456830.1
CX3CL1	ENST00000564948.1	c.71-2363C>A		intron_variant	Intron 1 of 1	3		ENSP00000457996.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	0.0010
DANN	Benign	0.90
DEOGEN2	Benign	0.32	T;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.46	T;T
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.36	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L;.
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.3	N;N
REVEL	Benign	0.049
Sift	Benign	0.35	T;T
Sift4G	Benign	0.34	T;T
Polyphen		0.023	B;.
Vest4		0.22
MutPred		0.69		Gain of methylation at T35 (P = 0.0037);.;
MVP		0.17
MPC		0.38
ClinPred		0.18	T
GERP RS		-6.3
Varity_R		0.28
gMVP		0.78

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: chr16-57413579;