Variant 19-41220693-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_021913.5(AXL):c.143G>C(p.Arg48Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,654 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

AXL
NM_021913.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.87

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AXL	NM_021913.5 linkuse as main transcript	c.143G>C	p.Arg48Pro	missense_variant	2/20	ENST00000301178.9	NP_068713.2
AXL	NM_001699.6 linkuse as main transcript	c.143G>C	p.Arg48Pro	missense_variant	2/19		NP_001690.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AXL	ENST00000301178.9 linkuse as main transcript	c.143G>C	p.Arg48Pro	missense_variant	2/20	1	NM_021913.5	ENSP00000301178	A2	P30530-1
AXL	ENST00000359092.7 linkuse as main transcript	c.143G>C	p.Arg48Pro	missense_variant	2/19	1		ENSP00000351995	P2	P30530-2
AXL	ENST00000599659.5 linkuse as main transcript	n.157G>C		non_coding_transcript_exon_variant	2/12	1
AXL	ENST00000594880.1 linkuse as main transcript	n.160G>C		non_coding_transcript_exon_variant	2/4	4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1459654

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725942

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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 18, 2021

The c.143G>C (p.R48P) alteration is located in exon 2 (coding exon 2) of the AXL gene. This alteration results from a G to C substitution at nucleotide position 143, causing the arginine (R) at amino acid position 48 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Uncertain

0.090

BayesDel_noAF

Benign

-0.11

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.19

T;.

Eigen

Uncertain

0.32

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.85

T;T

M_CAP

Benign

0.079

MetaRNN

Uncertain

0.66

D;D

MetaSVM

Benign

-0.58

MutationAssessor

Benign

1.2

L;L

MutationTaster

Benign

0.77

N;N

PrimateAI

Benign

0.45

PROVEAN

Benign

-2.2

N;N

REVEL

Uncertain

0.39

Sift

Uncertain

0.023

D;D

Sift4G

Benign

0.097

T;T

Polyphen

1.0

D;D

Vest4

0.56

MutPred

0.63

Loss of methylation at R48 (P = 0.0126);Loss of methylation at R48 (P = 0.0126);

MVP

0.64

MPC

1.1

ClinPred

0.91

GERP RS

4.6

Varity_R

0.68

gMVP

0.60

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over