16-57382055-T-C

Variant names:

• chr16-57382055-T-C
• NM_002996.6:c.217T>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_002996.6(CX3CL1):​c.217T>C​(p.Phe73Leu) 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. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CX3CL1 NM_002996.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0570
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36187845).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002996.6. 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
	CX3CL1	NM_002996.6	MANE Select	c.217T>C	p.Phe73Leu	missense	Exon 3 of 3	NP_002987.1	P78423
	CX3CL1	NM_001304392.3		c.-39T>C		5_prime_UTR	Exon 2 of 2	NP_001291321.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CX3CL1	ENST00000006053.7	TSL:1 MANE Select	c.217T>C	p.Phe73Leu	missense	Exon 3 of 3	ENSP00000006053.6	P78423
	CX3CL1	ENST00000565912.1	TSL:1	c.103T>C	p.Phe35Leu	missense	Exon 2 of 2	ENSP00000464114.1	J3QRA1
	CX3CL1	ENST00000563383.1	TSL:5	c.235T>C	p.Phe79Leu	missense	Exon 3 of 3	ENSP00000456830.1	H3BSR6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

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	Pathogenic	0.90
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	9.9
DANN	Benign	0.92
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.47
FATHMM_MKL	Benign	0.089	N
LIST_S2	Benign	0.55	T
M_CAP	Benign	0.0075	T
MetaRNN	Benign	0.36	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.057
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.089
Sift	Uncertain	0.027	D
Sift4G	Benign	0.090	T
Polyphen		0.32	B
Vest4		0.29
MutPred		0.51		Loss of sheet (P = 0.0228)
MVP		0.043
MPC		0.59
ClinPred		0.44	T
GERP RS		2.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.35
gMVP		0.92

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

hg19: chr16-57415967;