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GeneBe

3-46021627-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001024644.2(XCR1):c.321G>T(p.Met107Ile) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

XCR1
NM_001024644.2 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.04
Variant links:
Genes affected
XCR1 (HGNC:1625): (X-C motif chemokine receptor 1) The protein encoded by this gene is a chemokine receptor belonging to the G protein-coupled receptor superfamily. The family members are characterized by the presence of 7 transmembrane domains. The encoded protein transduces a signal by increasing the intracellular calcium ion level. The viral macrophage inflammatory protein-II is an antagonist of this receptor and blocks signaling. Some studies have implicated a cluster of genes at 3p21.31, including this gene, as associated with COVID-19 risk. The encoded protein may also play a role in cell proliferation and migration in several types of cancer. [provided by RefSeq, Jan 2023]

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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=0.09065953).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
XCR1NM_001024644.2 linkuse as main transcriptc.321G>T p.Met107Ile missense_variant 2/2 ENST00000309285.4
XCR1NM_001381860.1 linkuse as main transcriptc.321G>T p.Met107Ile missense_variant 4/4
XCR1NM_005283.3 linkuse as main transcriptc.321G>T p.Met107Ile missense_variant 3/3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
XCR1ENST00000309285.4 linkuse as main transcriptc.321G>T p.Met107Ile missense_variant 2/21 NM_001024644.2 P1
XCR1ENST00000395946.3 linkuse as main transcriptc.321G>T p.Met107Ile missense_variant 3/31 P1
XCR1ENST00000683768.1 linkuse as main transcriptc.321G>T p.Met107Ile missense_variant 6/6 P1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32

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 GeneticsJan 03, 2024The c.321G>T (p.M107I) alteration is located in exon 3 (coding exon 1) of the XCR1 gene. This alteration results from a G to T substitution at nucleotide position 321, causing the methionine (M) at amino acid position 107 to be replaced by an isoleucine (I). 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
Uncertain
0.50
BayesDel_addAF
Benign
-0.20
T
BayesDel_noAF
Benign
-0.52
Cadd
Benign
15
Dann
Benign
0.92
DEOGEN2
Benign
0.095
T
Eigen
Benign
-0.34
Eigen_PC
Benign
-0.30
FATHMM_MKL
Benign
0.10
N
LIST_S2
Benign
0.75
T
M_CAP
Benign
0.0070
T
MetaRNN
Benign
0.091
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.4
L
MutationTaster
Benign
1.0
N;N
PrimateAI
Benign
0.39
T
PROVEAN
Benign
-1.3
N
REVEL
Benign
0.050
Sift
Benign
0.28
T
Sift4G
Benign
0.39
T
Polyphen
0.25
B
Vest4
0.27
MutPred
0.52
Loss of ubiquitination at K103 (P = 0.1647);
MVP
0.24
MPC
0.61
ClinPred
0.33
T
GERP RS
3.7
Varity_R
0.13
gMVP
0.32

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-46063119; API