Variant 15-41564203-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_006293.4(TYRO3):c.600G>A(p.Met200Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000131 in 1,614,028 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

TYRO3
NM_006293.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.34

Variant links:

Genes affected

TYRO3 (HGNC:12446): (TYRO3 protein tyrosine kinase) The gene is part of a 3-member transmembrane receptor kinase receptor family with a processed pseudogene distal on chromosome 15. The encoded protein is activated by the products of the growth arrest-specific gene 6 and protein S genes and is involved in controlling cell survival and proliferation, spermatogenesis, immunoregulation and phagocytosis. The encoded protein has also been identified as a cell entry factor for Ebola and Marburg viruses. [provided by RefSeq, May 2010]

TYRO3 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=0.075519145).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TYRO3	NM_006293.4 link	c.600G>A	p.Met200Ile	missense_variant	5/19	ENST00000263798.8	NP_006284.2	Q06418
TYRO3	NM_001330264.2 link	c.465G>A	p.Met155Ile	missense_variant	5/19		NP_001317193.1	Q06418H0YNK6
TYRO3	XM_017022543.3 link	c.600G>A	p.Met200Ile	missense_variant	5/19		XP_016878032.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TYRO3	ENST00000263798.8 link	c.600G>A	p.Met200Ile	missense_variant	5/19	1	NM_006293.4	ENSP00000263798.3		Q06418
TYRO3	ENST00000559066.5 link	c.465G>A	p.Met155Ile	missense_variant	5/19	5		ENSP00000454050.1		H0YNK6

Frequencies

GnomAD3 genomes

AF:

0.0000788

AC:

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000118

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000596

AC:

AN:

251476

Hom.:

AF XY:

0.0000736

AC XY:

AN XY:

135920

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00

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:

0.000105

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000136

AC:

199

AN:

1461840

Hom.:

Cov.:

AF XY:

0.000131

AC XY:

AN XY:

727216

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

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:

0.000174

Gnomad4 OTH exome

AF:

0.0000828

GnomAD4 genome

AF:

0.0000788

AC:

AN:

152188

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.0000965

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000103

Hom.:

Bravo

AF:

0.0000945

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000412

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

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 03, 2022

The c.600G>A (p.M200I) alteration is located in exon 5 (coding exon 5) of the TYRO3 gene. This alteration results from a G to A substitution at nucleotide position 600, causing the methionine (M) at amino acid position 200 to be replaced by an isoleucine (I). 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

0.10

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.70

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.012

T;T

Eigen

Benign

-0.65

Eigen_PC

Benign

-0.49

FATHMM_MKL

Benign

0.64

LIST_S2

Uncertain

0.87

D;D

M_CAP

Benign

0.0086

MetaRNN

Benign

0.076

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.35

.;N

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.16

N;N

REVEL

Benign

0.041

Sift

Benign

0.38

T;T

Sift4G

Benign

0.21

T;T

Polyphen

0.0020

.;B

Vest4

0.29

MutPred

0.32

.;Gain of catalytic residue at S202 (P = 0.1156);

MVP

0.068

MPC

0.44

ClinPred

0.042

GERP RS

1.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.039

gMVP

0.25

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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