3-46021599-T-A
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001024644.2(XCR1):c.349A>T(p.Ile117Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000329 in 152,026 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
XCR1
NM_001024644.2 missense
NM_001024644.2 missense
Scores
3
9
7
Clinical Significance
Conservation
PhyloP100: 1.07
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 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
XCR1 | NM_001024644.2 | c.349A>T | p.Ile117Phe | missense_variant | 2/2 | ENST00000309285.4 | NP_001019815.1 | |
XCR1 | NM_001381860.1 | c.349A>T | p.Ile117Phe | missense_variant | 4/4 | NP_001368789.1 | ||
XCR1 | NM_005283.3 | c.349A>T | p.Ile117Phe | missense_variant | 3/3 | NP_005274.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
XCR1 | ENST00000309285.4 | c.349A>T | p.Ile117Phe | missense_variant | 2/2 | 1 | NM_001024644.2 | ENSP00000310405 | P1 | |
XCR1 | ENST00000395946.3 | c.349A>T | p.Ile117Phe | missense_variant | 3/3 | 1 | ENSP00000379277 | P1 | ||
XCR1 | ENST00000683768.1 | c.349A>T | p.Ile117Phe | missense_variant | 6/6 | ENSP00000507745 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152026Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000121 AC: 3AN: 248396Hom.: 0 AF XY: 0.00000745 AC XY: 1AN XY: 134246
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GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1460674Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 726514
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GnomAD4 genome AF: 0.0000329 AC: 5AN: 152026Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74266
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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 | Jan 30, 2024 | The c.349A>T (p.I117F) alteration is located in exon 3 (coding exon 1) of the XCR1 gene. This alteration results from a A to T substitution at nucleotide position 349, causing the isoleucine (I) at amino acid position 117 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Benign
D
MetaRNN
Uncertain
D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
H
MutationTaster
Benign
D;D
PrimateAI
Benign
T
PROVEAN
Uncertain
D
REVEL
Pathogenic
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MVP
MPC
ClinPred
D
GERP RS
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at