XCL2 p.Ser43Arg

Variant names:

• chr1-168542042-T-G
• NM_003175.4:c.127A>C
• XCL2 p.Ser43Arg

Your query was ambiguous. Multiple possible variants found:

• chr1-168542042-T-G
• chr1-168542040-G-T
• chr1-168542040-G-C
• chr1-168542040-GCT-ACG
• chr1-168542040-GCT-TCG
• chr1-168542040-GCT-CCG

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003175.4(XCL2):​c.127A>C​(p.Ser43Arg) 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. 16/22 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 30)
• Consequence: XCL2 NM_003175.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.169
• Publications: 0 publications found

Genes affected

XCL2 (HGNC:10646): (X-C motif chemokine ligand 2) Predicted to enable CCR chemokine receptor binding activity and chemokine activity. Predicted to be involved in several processes, including cellular response to cytokine stimulus; leukocyte chemotaxis; and positive regulation of T cell chemotaxis. Predicted to be located in extracellular region. Predicted to be active in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000307038 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.060885757).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003175.4. 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
	XCL2	NM_003175.4	MANE Select	c.127A>C	p.Ser43Arg	missense	Exon 2 of 3	NP_003166.1	Q9UBD3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XCL2	ENST00000367819.3	TSL:1 MANE Select	c.127A>C	p.Ser43Arg	missense	Exon 2 of 3	ENSP00000356793.2	Q9UBD3
	ENSG00000307038	ENST00000823032.1		n.313-34220T>G		intron	N/A
	ENSG00000307038	ENST00000823033.1		n.304-1845T>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	2.6
DANN	Benign	0.68
DEOGEN2	Benign	0.0050	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0063	N
LIST_S2	Benign	0.32	T
M_CAP	Benign	0.0047	T
MetaRNN	Benign	0.061	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.50	N
PhyloP100		-0.17
PrimateAI	Benign	0.31	T
PROVEAN	Benign	0.060	N
REVEL	Benign	0.015
Sift	Benign	0.50	T
Sift4G	Benign	0.20	T
Varity_R		0.056
gMVP		0.14
Mutation Taster		=96/4	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr1-168511280;