Variant 1-168541059-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_003175.4(XCL2):c.238G>A(p.Val80Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00027 in 1,613,568 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00030 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00027 ( 1 hom. )

Consequence

XCL2
NM_003175.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.74

Variant links:

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]

XCL2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06533575).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XCL2	NM_003175.4 linkuse as main transcript	c.238G>A	p.Val80Met	missense_variant	3/3	ENST00000367819.3	NP_003166.1	Q9UBD3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XCL2	ENST00000367819.3 linkuse as main transcript	c.238G>A	p.Val80Met	missense_variant	3/3	1	NM_003175.4	ENSP00000356793.2		Q9UBD3

Frequencies

GnomAD3 genomes

AF:

0.000296

AC:

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000459

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000367

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000231

AC:

AN:

250982

Hom.:

AF XY:

0.000199

AC XY:

AN XY:

135626

show subpopulations

Gnomad AFR exome

AF:

0.000800

Gnomad AMR exome

AF:

0.0000580

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.000323

Gnomad NFE exome

AF:

0.000300

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000268

AC:

391

AN:

1461390

Hom.:

Cov.:

AF XY:

0.000232

AC XY:

169

AN XY:

726994

show subpopulations

Gnomad4 AFR exome

AF:

0.000568

Gnomad4 AMR exome

AF:

0.0000448

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.000206

Gnomad4 NFE exome

AF:

0.000311

Gnomad4 OTH exome

AF:

0.000182

GnomAD4 genome

AF:

0.000296

AC:

AN:

152178

Hom.:

Cov.:

AF XY:

0.000309

AC XY:

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.000459

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.000367

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000392

Hom.:

Bravo

AF:

0.000306

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000239

AC:

EpiCase

AF:

0.000382

EpiControl

AF:

0.000296

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 18, 2023

The c.238G>A (p.V80M) alteration is located in exon 3 (coding exon 3) of the XCL2 gene. This alteration results from a G to A substitution at nucleotide position 238, causing the valine (V) at amino acid position 80 to be replaced by a methionine (M). 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

Benign

0.23

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.70

CADD

Benign

DANN

Benign

0.88

DEOGEN2

Benign

0.012

Eigen

Benign

-0.75

Eigen_PC

Benign

-0.84

FATHMM_MKL

Benign

0.041

LIST_S2

Benign

0.45

M_CAP

Benign

0.0048

MetaRNN

Benign

0.065

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.3

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.58

REVEL

Benign

0.048

Sift

Benign

0.21

Sift4G

Benign

0.22

Polyphen

0.44

Vest4

0.092

MVP

0.15

MPC

0.21

ClinPred

0.013

GERP RS

2.4

Varity_R

0.051

gMVP

0.19

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over