chr16-57382350-C-A

Variant names:

• chr16-57382350-C-A
• rs541210508
• NM_002996.6:c.512C>A

Variant summary

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

The NM_002996.6(CX3CL1):​c.512C>A​(p.Pro171Gln) 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 1,457,716 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P171L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CX3CL1 NM_002996.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.108

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08162129).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CX3CL1	NM_002996.6	c.512C>A	p.Pro171Gln	missense_variant	Exon 3 of 3	ENST00000006053.7	NP_002987.1
CX3CL1	NM_001304392.3	c.257C>A	p.Pro86Gln	missense_variant	Exon 2 of 2		NP_001291321.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CX3CL1	ENST00000006053.7	c.512C>A	p.Pro171Gln	missense_variant	Exon 3 of 3	1	NM_002996.6	ENSP00000006053.6
CX3CL1	ENST00000565912.1	c.398C>A	p.Pro133Gln	missense_variant	Exon 2 of 2	1		ENSP00000464114.1
CX3CL1	ENST00000563383.1	c.530C>A	p.Pro177Gln	missense_variant	Exon 3 of 3	5		ENSP00000456830.1
CX3CL1	ENST00000564948.1	c.*223C>A		3_prime_UTR_variant	Exon 2 of 2	3		ENSP00000457996.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1457716 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 725202

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	2.7
DANN	Benign	0.84
DEOGEN2	Benign	0.25	T;T;.
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.58	T;T;T
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.082	T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.90	L;.;.
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.15	N;N;.
REVEL	Benign	0.088
Sift	Benign	0.11	T;T;.
Sift4G	Benign	0.15	T;T;T
Polyphen		0.16	B;.;.
Vest4		0.10
MutPred		0.18		Loss of catalytic residue at P170 (P = 0.0165);.;.;
MVP		0.043
MPC		0.54
ClinPred		0.43	T
GERP RS		3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.039
gMVP		0.14

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: rs541210508; hg19: chr16-57416262;