rs1000076660

Variant summary

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

The NM_021913.5(AXL):​c.80C>A​(p.Pro27His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000276 in 1,451,864 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P27L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

AXL
NM_021913.5 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.772
Variant links:
Genes affected
AXL (HGNC:905): (AXL receptor tyrosine kinase) The protein encoded by this gene is a member of the Tyro3-Axl-Mer (TAM) receptor tyrosine kinase subfamily. The encoded protein possesses an extracellular domain which is composed of two immunoglobulin-like motifs at the N-terminal, followed by two fibronectin type-III motifs. It transduces signals from the extracellular matrix into the cytoplasm by binding to the vitamin K-dependent protein growth arrest-specific 6 (Gas6). This gene may be involved in several cellular functions including growth, migration, aggregation and anti-inflammation in multiple cell types. The encoded protein acts as a host cell receptor for multiple viruses, including Marburg, Ebola and Lassa viruses and is a candidate receptor for the SARS-CoV2 virus. [provided by RefSeq, Sep 2021]

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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=0.07326299).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
AXLNM_021913.5 linkc.80C>A p.Pro27His missense_variant Exon 1 of 20 ENST00000301178.9 NP_068713.2 P30530-1
AXLNM_001699.6 linkc.80C>A p.Pro27His missense_variant Exon 1 of 19 NP_001690.2 P30530-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
AXLENST00000301178.9 linkc.80C>A p.Pro27His missense_variant Exon 1 of 20 1 NM_021913.5 ENSP00000301178.3 P30530-1
AXLENST00000359092.7 linkc.80C>A p.Pro27His missense_variant Exon 1 of 19 1 ENSP00000351995.2 P30530-2
AXLENST00000599659.5 linkn.94C>A non_coding_transcript_exon_variant Exon 1 of 12 1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
0.00000276
AC:
4
AN:
1451864
Hom.:
0
Cov.:
38
AF XY:
0.00000139
AC XY:
1
AN XY:
721334
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000102
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.096
T
BayesDel_noAF
Benign
-0.38
CADD
Benign
13
DANN
Benign
0.89
DEOGEN2
Benign
0.19
T;.
Eigen
Benign
-0.93
Eigen_PC
Benign
-0.89
FATHMM_MKL
Benign
0.10
N
LIST_S2
Benign
0.55
T;T
M_CAP
Benign
0.037
D
MetaRNN
Benign
0.073
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.0
N;N
PrimateAI
Benign
0.43
T
PROVEAN
Benign
-1.3
N;N
REVEL
Benign
0.081
Sift
Benign
0.16
T;T
Sift4G
Benign
0.58
T;T
Polyphen
0.0010
B;B
Vest4
0.31
MutPred
0.47
Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);
MVP
0.14
MPC
0.30
ClinPred
0.063
T
GERP RS
0.80
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0
Varity_R
0.037
gMVP
0.33

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1000076660; hg19: chr19-41725377; API