rs1175570418

Variant names:

• chr19-41220661-C-G
• NM_021913.5:c.111C>G

Your query was ambiguous. Multiple possible variants found:

• chr19-41220661-C-G
• chr19-41220661-C-T

Variant summary

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

The NM_021913.5(AXL):​c.111C>G​(p.Phe37Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. F37F) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: AXL NM_021913.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28

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]

ACMG classification

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 rank	MANE	Protein	UniProt
AXL	NM_021913.5	c.111C>G	p.Phe37Leu	missense_variant	Exon 2 of 20	ENST00000301178.9	NP_068713.2
AXL	NM_001699.6	c.111C>G	p.Phe37Leu	missense_variant	Exon 2 of 19		NP_001690.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AXL	ENST00000301178.9	c.111C>G	p.Phe37Leu	missense_variant	Exon 2 of 20	1	NM_021913.5	ENSP00000301178.3
AXL	ENST00000359092.7	c.111C>G	p.Phe37Leu	missense_variant	Exon 2 of 19	1		ENSP00000351995.2
AXL	ENST00000599659.5	n.125C>G		non_coding_transcript_exon_variant	Exon 2 of 12	1
AXL	ENST00000594880.1	n.128C>G		non_coding_transcript_exon_variant	Exon 2 of 4	4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	9.9
DANN	Benign	0.91
DEOGEN2	Benign	0.34	T;.
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.54
FATHMM_MKL	Benign	0.066	N
LIST_S2	Benign	0.78	T;T
M_CAP	Benign	0.0076	T
MetaRNN	Uncertain	0.65	D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M;M
PrimateAI	Uncertain	0.52	T
PROVEAN	Uncertain	-2.5	D;D
REVEL	Benign	0.19
Sift	Benign	0.40	T;T
Sift4G	Benign	0.49	T;T
Polyphen		1.0	D;D
Vest4		0.67
MutPred		0.48		Gain of disorder (P = 0.1003);Gain of disorder (P = 0.1003);
MVP		0.16
MPC		0.99
ClinPred		0.92	D
GERP RS		1.0
Varity_R		0.30
gMVP		0.79

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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.

Other links and lift over

hg19: chr19-41726566;