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GeneBe

1-168581159-T-C

Variant summary

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

The NM_002995.3(XCL1):c.284T>C(p.Ile95Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,613,604 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 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

XCL1
NM_002995.3 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -4.24
Variant links:
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]

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=0.03030029).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
XCL1NM_002995.3 linkuse as main transcriptc.284T>C p.Ile95Thr missense_variant 3/3 ENST00000367818.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
XCL1ENST00000367818.4 linkuse as main transcriptc.284T>C p.Ile95Thr missense_variant 3/31 NM_002995.3 P1

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152054
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000725
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:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
250990
Hom.:
0
AF XY:
0.00000737
AC XY:
1
AN XY:
135644
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000882
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000274
AC:
4
AN:
1461550
Hom.:
0
Cov.:
30
AF XY:
0.00000275
AC XY:
2
AN XY:
727080
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000270
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152054
Hom.:
0
Cov.:
32
AF XY:
0.0000404
AC XY:
3
AN XY:
74284
show subpopulations
Gnomad4 AFR
AF:
0.0000725
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000567
ExAC
AF:
0.00000824
AC:
1

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 submitterclinical testingAmbry GeneticsMar 01, 2024The c.284T>C (p.I95T) alteration is located in exon 3 (coding exon 3) of the XCL1 gene. This alteration results from a T to C substitution at nucleotide position 284, causing the isoleucine (I) at amino acid position 95 to be replaced by a threonine (T). 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
0.10
BayesDel_addAF
Benign
-0.42
T
BayesDel_noAF
Benign
-0.84
Cadd
Benign
0.0030
Dann
Benign
0.43
DEOGEN2
Benign
0.041
T
Eigen
Benign
-2.0
Eigen_PC
Benign
-2.1
FATHMM_MKL
Benign
0.0027
N
LIST_S2
Benign
0.41
T
M_CAP
Benign
0.0017
T
MetaRNN
Benign
0.030
T
MetaSVM
Benign
-0.97
T
MutationAssessor
Benign
-1.2
N
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.29
T
PROVEAN
Benign
0.37
N
REVEL
Benign
0.019
Sift
Benign
0.88
T
Sift4G
Benign
1.0
T
Polyphen
0.0
B
Vest4
0.026
MutPred
0.18
Loss of stability (P = 0.0213);
MVP
0.014
MPC
0.089
ClinPred
0.036
T
GERP RS
-9.7
Varity_R
0.018
gMVP
0.083

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.

Other links and lift over

dbSNP: rs751966135; hg19: chr1-168550397; API