chr11-57236647-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_005161.6(APLNR):c.358C>A(p.Leu120Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000055 in 1,455,830 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000055 ( 0 hom. )
Consequence
APLNR
NM_005161.6 missense
NM_005161.6 missense
Scores
7
4
4
Clinical Significance
Conservation
PhyloP100: 6.82
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 3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.787
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
APLNR | NM_005161.6 | c.358C>A | p.Leu120Ile | missense_variant | 1/1 | ENST00000606794.2 | |
APLNR | NR_027991.2 | n.604C>A | non_coding_transcript_exon_variant | 1/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
APLNR | ENST00000606794.2 | c.358C>A | p.Leu120Ile | missense_variant | 1/1 | NM_005161.6 | P1 | ||
APLNR | ENST00000257254.3 | c.358C>A | p.Leu120Ile | missense_variant, NMD_transcript_variant | 1/2 | 1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD4 exome AF: 0.00000550 AC: 8AN: 1455830Hom.: 0 Cov.: 29 AF XY: 0.00000414 AC XY: 3AN XY: 724196
GnomAD4 exome
AF:
AC:
8
AN:
1455830
Hom.:
Cov.:
29
AF XY:
AC XY:
3
AN XY:
724196
Gnomad4 AFR exome
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GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
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 | Oct 27, 2022 | The c.358C>A (p.L120I) alteration is located in exon 1 (coding exon 1) of the APLNR gene. This alteration results from a C to A substitution at nucleotide position 358, causing the leucine (L) at amino acid position 120 to be replaced by an isoleucine (I). 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
Pathogenic
D
BayesDel_noAF
Uncertain
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Benign
T;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M;M
MutationTaster
Benign
D
PrimateAI
Pathogenic
D
Sift4G
Benign
T;T
Polyphen
D;D
Vest4
MutPred
Loss of helix (P = 0.2271);Loss of helix (P = 0.2271);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.