2-236580949-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_020311.3(ACKR3):c.484C>T(p.Arg162Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000031 in 1,614,060 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000033 ( 1 hom. )
Consequence
ACKR3
NM_020311.3 missense
NM_020311.3 missense
Scores
1
7
10
Clinical Significance
Conservation
PhyloP100: 3.80
Genes affected
ACKR3 (HGNC:23692): (atypical chemokine receptor 3) This gene encodes a member of the G-protein coupled receptor family. Although this protein was earlier thought to be a receptor for vasoactive intestinal peptide (VIP), it is now considered to be an orphan receptor, in that its endogenous ligand has not been identified. The protein is also a coreceptor for human immunodeficiency viruses (HIV). Translocations involving this gene and HMGA2 on chromosome 12 have been observed in lipomas. [provided by RefSeq, Jul 2008]
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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 | UniProt |
---|---|---|---|---|---|---|---|
ACKR3 | NM_020311.3 | c.484C>T | p.Arg162Cys | missense_variant | 2/2 | ENST00000272928.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ACKR3 | ENST00000272928.4 | c.484C>T | p.Arg162Cys | missense_variant | 2/2 | 2 | NM_020311.3 | P1 | |
ACKR3 | ENST00000447924.1 | c.484C>T | p.Arg162Cys | missense_variant | 2/2 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152188Hom.: 0 Cov.: 33
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000438 AC: 11AN: 251414Hom.: 0 AF XY: 0.0000515 AC XY: 7AN XY: 135888
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GnomAD4 exome AF: 0.0000328 AC: 48AN: 1461872Hom.: 1 Cov.: 31 AF XY: 0.0000344 AC XY: 25AN XY: 727240
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GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152188Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74358
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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 | Dec 21, 2022 | The c.484C>T (p.R162C) alteration is located in exon 2 (coding exon 1) of the ACKR3 gene. This alteration results from a C to T substitution at nucleotide position 484, causing the arginine (R) at amino acid position 162 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
T
MetaRNN
Uncertain
D;D
MetaSVM
Benign
T
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D
REVEL
Benign
Sift
Uncertain
D;D
Sift4G
Uncertain
T;D
Polyphen
0.16
.;B
Vest4
0.33
MutPred
Loss of MoRF binding (P = 0.0191);Loss of MoRF binding (P = 0.0191);
MVP
MPC
0.78
ClinPred
T
GERP RS
Varity_R
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