chr11-57236577-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_005161.6(APLNR):c.428G>A(p.Arg143Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000137 in 1,612,904 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00014 ( 1 hom. )
Consequence
APLNR
NM_005161.6 missense
NM_005161.6 missense
Scores
5
10
Clinical Significance
Conservation
PhyloP100: 2.06
Genes affected
APLNR (HGNC:339): (apelin receptor) This gene encodes a member of the G protein-coupled receptor gene family. The encoded protein is related to the angiotensin receptor, but is actually an apelin receptor that inhibits adenylate cyclase activity and plays a counter-regulatory role against the pressure action of angiotensin II by exerting hypertensive effect. It functions in the cardiovascular and central nervous systems, in glucose metabolism, in embryonic and tumor angiogenesis and as a human immunodeficiency virus (HIV-1) coreceptor. Two transcript variants resulting from alternative splicing have been identified. [provided by RefSeq, Jul 2009]
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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=0.092460275).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
APLNR | NM_005161.6 | c.428G>A | p.Arg143Gln | missense_variant | 1/1 | ENST00000606794.2 | |
APLNR | NR_027991.2 | n.674G>A | non_coding_transcript_exon_variant | 1/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
APLNR | ENST00000606794.2 | c.428G>A | p.Arg143Gln | missense_variant | 1/1 | NM_005161.6 | P1 | ||
APLNR | ENST00000257254.3 | c.428G>A | p.Arg143Gln | missense_variant, NMD_transcript_variant | 1/2 | 1 |
Frequencies
GnomAD3 genomes AF: 0.000131 AC: 20AN: 152232Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000231 AC: 57AN: 247252Hom.: 1 AF XY: 0.000239 AC XY: 32AN XY: 134170
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GnomAD4 exome AF: 0.000138 AC: 201AN: 1460672Hom.: 1 Cov.: 30 AF XY: 0.000142 AC XY: 103AN XY: 726688
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GnomAD4 genome AF: 0.000131 AC: 20AN: 152232Hom.: 0 Cov.: 33 AF XY: 0.000148 AC XY: 11AN XY: 74372
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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 | Jul 20, 2022 | The c.428G>A (p.R143Q) alteration is located in exon 1 (coding exon 1) of the APLNR gene. This alteration results from a G to A substitution at nucleotide position 428, causing the arginine (R) at amino acid position 143 to be replaced by a glutamine (Q). 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
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Benign
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L
MutationTaster
Benign
D
PrimateAI
Uncertain
T
Sift4G
Benign
T;T
Polyphen
P;P
Vest4
MVP
MPC
ClinPred
T
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