Genetic Variant TYRO3:p.Pro10Ser (chr15-41559285-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006293.4(TYRO3):c.28C>T(p.Pro10Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 35)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TYRO3
NM_006293.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.799

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1594573).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006293.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TYRO3	NM_006293.4	MANE Select	c.28C>T	p.Pro10Ser	missense	Exon 1 of 19	NP_006284.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TYRO3	ENST00000263798.8	TSL:1 MANE Select	c.28C>T	p.Pro10Ser	missense	Exon 1 of 19	ENSP00000263798.3	Q06418
TYRO3	ENST00000869540.1		c.28C>T	p.Pro10Ser	missense	Exon 1 of 20	ENSP00000539599.1
TYRO3	ENST00000869541.1		c.28C>T	p.Pro10Ser	missense	Exon 1 of 20	ENSP00000539600.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

384648

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

193712

African (AFR)

AF:

0.00

AC:

AN:

5952

American (AMR)

AF:

0.00

AC:

AN:

6076

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

8738

East Asian (EAS)

AF:

0.00

AC:

AN:

16400

South Asian (SAS)

AF:

0.00

AC:

AN:

7426

European-Finnish (FIN)

AF:

0.00

AC:

AN:

22676

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1452

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

297328

Other (OTH)

AF:

0.00

AC:

AN:

18600

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.15

Eigen

Benign

-0.89

Eigen_PC

Benign

-0.85

FATHMM_MKL

Benign

0.38

LIST_S2

Benign

0.44

M_CAP

Pathogenic

0.65

MetaRNN

Benign

0.16

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.63

PhyloP100

0.80

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-0.54

REVEL

Benign

0.071

Sift

Benign

0.14

Sift4G

Benign

0.079

Polyphen

0.0

Vest4

0.089

MutPred

0.25

Gain of phosphorylation at P10 (P = 0.0058)

MVP

0.16

MPC

0.39

ClinPred

0.065

GERP RS

1.6

PromoterAI

-0.018

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.056

gMVP

0.43

Mutation Taster

=95/5

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over