rs148500645

Variant names:

• chr1-168540975-T-A
• rs148500645
• NM_003175.4:c.322A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_003175.4(XCL2):​c.322A>T​(p.Thr108Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000323 in 1,613,494 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00024 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00033 (0 hom.)
• Consequence: XCL2 NM_003175.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.589
• Publications: 1 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.

• BP4: Computational evidence support a benign effect (MetaRNN=0.06977442).

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.322A>T	p.Thr108Ser	missense	Exon 3 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.322A>T	p.Thr108Ser	missense	Exon 3 of 3	ENSP00000356793.2	Q9UBD3
	ENSG00000307038	ENST00000823032.1		n.313-35287T>A		intron	N/A
	ENSG00000307038	ENST00000823033.1		n.304-2912T>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000243 AC: 37 AN: 152130 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000456

Gnomad OTH AF: 0.000955

GnomAD2 exomes AF: 0.000140 AC: 35 AN: 250866 AF XY: 0.000140

Gnomad AFR exome AF: 0.0000616

Gnomad AMR exome AF: 0.0000870

Gnomad ASJ exome AF: 0.000199

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000247

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000331 AC: 484 AN: 1461364 Hom.: 0 Cov.: 32 AF XY: 0.000307 AC XY: 223 AN XY: 726986

African (AFR) AF: 0.0000299 AC: 1 AN: 33444

American (AMR) AF: 0.0000672 AC: 3 AN: 44664

Ashkenazi Jewish (ASJ) AF: 0.000574 AC: 15 AN: 26116

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86238

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.000398 AC: 442 AN: 1111674

Other (OTH) AF: 0.000381 AC: 23 AN: 60364

GnomAD4 genome AF: 0.000243 AC: 37 AN: 152130 Hom.: 0 Cov.: 32 AF XY: 0.000215 AC XY: 16 AN XY: 74314

African (AFR) AF: 0.0000483 AC: 2 AN: 41446

American (AMR) AF: 0.000131 AC: 2 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000456 AC: 31 AN: 68008

Other (OTH) AF: 0.000955 AC: 2 AN: 2094

Alfa AF: 0.000313 Hom.: 0

Bravo AF: 0.000238

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.000124 AC: 15

EpiCase AF: 0.0000546

EpiControl AF: 0.000356

ClinVar

ClinVar submissions

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	Benign	0.094
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	6.1
DANN	Benign	0.90
DEOGEN2	Benign	0.0075	T
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.66
FATHMM_MKL	Benign	0.032	N
LIST_S2	Benign	0.47	T
M_CAP	Benign	0.0026	T
MetaRNN	Benign	0.070	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.8	L
PhyloP100		0.59
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.92	N
REVEL	Benign	0.059
Sift	Benign	0.046	D
Sift4G	Benign	0.21	T
Polyphen		0.90	P
Vest4		0.061
MVP		0.12
MPC		0.18
ClinPred		0.029	T
GERP RS		2.4
Varity_R		0.11
gMVP		0.11
Mutation Taster		=98/2	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

Other links and lift over

dbSNP: rs148500645; hg19: chr1-168510213;