dbSNP rs1000076660: AXL:p.Pro27His (chr19-41219472-C-A) – ACMG Classification: Uncertain_significance (0 pts)

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

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]

AXL links:

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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
AXL	NM_021913.5 link	c.80C>A	p.Pro27His	missense_variant	Exon 1 of 20	ENST00000301178.9	NP_068713.2	P30530-1
AXL	NM_001699.6 link	c.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	UniProt
AXL	ENST00000301178.9 link	c.80C>A	p.Pro27His	missense_variant	Exon 1 of 20	1	NM_021913.5	ENSP00000301178.3	P30530-1
AXL	ENST00000359092.7 link	c.80C>A	p.Pro27His	missense_variant	Exon 1 of 19	1		ENSP00000351995.2	P30530-2
AXL	ENST00000599659.5 link	n.94C>A		non_coding_transcript_exon_variant	Exon 1 of 12	1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000276

AC:

AN:

1451864

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

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.:

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

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Benign

0.89

DEOGEN2

Benign

0.19

T;.

Eigen

Benign

-0.93

Eigen_PC

Benign

-0.89

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.55

T;T

M_CAP

Benign

0.037

MetaRNN

Benign

0.073

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;N

PrimateAI

Benign

0.43

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

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

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