Variant 1-168540975-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00033 ( 0 hom. )

Consequence

XCL2
NM_003175.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.589

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XCL2	NM_003175.4 link	c.322A>T	p.Thr108Ser	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 link	c.322A>T	p.Thr108Ser	missense_variant	3/3	1	NM_003175.4	ENSP00000356793.2		Q9UBD3

Frequencies

GnomAD3 genomes

AF:

0.000243

AC:

AN:

152130

Hom.:

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.000140

AC:

AN:

250866

Hom.:

AF XY:

0.000140

AC XY:

AN XY:

135562

show subpopulations

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 SAS 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.:

Cov.:

AF XY:

0.000307

AC XY:

223

AN XY:

726986

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000672

Gnomad4 ASJ exome

AF:

0.000574

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000398

Gnomad4 OTH exome

AF:

0.000381

GnomAD4 genome

AF:

0.000243

AC:

AN:

152130

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000456

Gnomad4 OTH

AF:

0.000955

Alfa

AF:

0.000313

Hom.:

Bravo

AF:

0.000238

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000124

AC:

EpiCase

AF:

0.0000546

EpiControl

AF:

0.000356

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

Jul 02, 2024

The c.322A>T (p.T108S) alteration is located in exon 3 (coding exon 3) of the XCL2 gene. This alteration results from a A to T substitution at nucleotide position 322, causing the threonine (T) at amino acid position 108 to be replaced by a serine (S). 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

0.094

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.70

CADD

Benign

6.1

DANN

Benign

0.90

DEOGEN2

Benign

0.0075

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.66

FATHMM_MKL

Benign

0.032

LIST_S2

Benign

0.47

M_CAP

Benign

0.0026

MetaRNN

Benign

0.070

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.8

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.92

REVEL

Benign

0.059

Sift

Benign

0.046

Sift4G

Benign

0.21

Polyphen

0.90

Vest4

0.061

MVP

0.12

MPC

0.18

ClinPred

0.029

GERP RS

2.4

Varity_R

0.11

gMVP

0.11

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