Variant 19-41219445-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_021913.5(AXL):c.53C>T(p.Ala18Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000135 in 1,606,016 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. A18A) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00075 ( 1 hom., cov: 31)

Exomes 𝑓: 0.000072 ( 0 hom. )

Consequence

AXL
NM_021913.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.48

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003844887).

BP6

Variant 19-41219445-C-T is Benign according to our data. Variant chr19-41219445-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 720601.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 113 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AXL	NM_021913.5 linkuse as main transcript	c.53C>T	p.Ala18Val	missense_variant	1/20	ENST00000301178.9
AXL	NM_001699.6 linkuse as main transcript	c.53C>T	p.Ala18Val	missense_variant	1/19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AXL	ENST00000301178.9 linkuse as main transcript	c.53C>T	p.Ala18Val	missense_variant	1/20	1	NM_021913.5	A2	P30530-1
AXL	ENST00000359092.7 linkuse as main transcript	c.53C>T	p.Ala18Val	missense_variant	1/19	1		P2	P30530-2
AXL	ENST00000599659.5 linkuse as main transcript	n.67C>T		non_coding_transcript_exon_variant	1/12	1

Frequencies

GnomAD3 genomes

AF:

0.000752

AC:

114

AN:

151540

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00257

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000263

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000442

Gnomad OTH

AF:

0.000480

GnomAD3 exomes

AF:

0.000244

AC:

AN:

229768

Hom.:

AF XY:

0.000200

AC XY:

AN XY:

125172

show subpopulations

Gnomad AFR exome

AF:

0.00293

Gnomad AMR exome

AF:

0.000391

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000197

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000715

AC:

104

AN:

1454362

Hom.:

Cov.:

AF XY:

0.0000706

AC XY:

AN XY:

722870

show subpopulations

Gnomad4 AFR exome

AF:

0.00198

Gnomad4 AMR exome

AF:

0.000410

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:

0.00000721

Gnomad4 OTH exome

AF:

0.000200

GnomAD4 genome

AF:

0.000745

AC:

113

AN:

151654

Hom.:

Cov.:

AF XY:

0.000634

AC XY:

AN XY:

74110

show subpopulations

Gnomad4 AFR

AF:

0.00254

Gnomad4 AMR

AF:

0.000263

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000442

Gnomad4 OTH

AF:

0.000475

Alfa

AF:

0.000475

Hom.:

Bravo

AF:

0.000850

ESP6500AA

AF:

0.00297

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000273

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

May 14, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.48

CADD

Benign

1.3

DANN

Benign

0.94

DEOGEN2

Benign

0.19

T;.

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.025

LIST_S2

Benign

0.68

T;T

M_CAP

Benign

0.058

MetaRNN

Benign

0.0038

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

N;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.43

PROVEAN

Benign

0.030

N;N

REVEL

Benign

0.039

Sift

Benign

0.19

T;T

Sift4G

Benign

0.67

T;T

Polyphen

0.0080

B;B

Vest4

0.19

MVP

0.18

MPC

0.25

ClinPred

0.0047

GERP RS

-6.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.025

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over