NM_002995.3:c.23T>C

Variant names:

• chr1-168576660-T-C
• NM_002995.3:c.23T>C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_002995.3(XCL1):​c.23T>C​(p.Leu8Pro) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: XCL1 NM_002995.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.672

Genes affected

XCL1 (HGNC:10645): (X-C motif chemokine ligand 1) This antimicrobial gene encodes a member of the chemokine superfamily. Chemokines function in inflammatory and immunological responses, inducing leukocyte migration and activation. The encoded protein is a member of the C-chemokine subfamily, retaining only two of four cysteines conserved in other chemokines, and is thought to be specifically chemotactic for T cells. This gene and a closely related family member are located on the long arm of chromosome 1. [provided by RefSeq, Sep 2014]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.866

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XCL1	NM_002995.3	c.23T>C	p.Leu8Pro	missense_variant	Exon 1 of 3	ENST00000367818.4	NP_002986.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XCL1	ENST00000367818.4	c.23T>C	p.Leu8Pro	missense_variant	Exon 1 of 3	1	NM_002995.3	ENSP00000356792.3

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 30

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 08, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.23T>C (p.L8P) alteration is located in exon 1 (coding exon 1) of the XCL1 gene. This alteration results from a T to C substitution at nucleotide position 23, causing the leucine (L) at amino acid position 8 to be replaced by a proline (P). 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	Uncertain	0.43
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	18
DANN	Benign	0.70
DEOGEN2	Uncertain	0.55	D
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.037	N
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.0037	T
MetaRNN	Pathogenic	0.87	D
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.3	M
PrimateAI	Benign	0.27	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.20
Sift	Uncertain	0.019	D
Sift4G	Uncertain	0.035	D
Polyphen		0.94	P
Vest4		0.59
MutPred		0.72		Loss of stability (P = 0.0084);
MVP		0.061
MPC		0.12
ClinPred		0.79	D
GERP RS		-0.036
Varity_R		0.51
gMVP		0.64

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: chr1-168545898;