Genetic Variant TYRO3:p.Gly421Val (chr15-41570036-G-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.1262G>T(p.Gly421Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000342 in 1,460,488 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

TYRO3
NM_006293.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.66

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=0.11064789).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TYRO3	NM_006293.4 link	c.1262G>T	p.Gly421Val	missense_variant	Exon 10 of 19	ENST00000263798.8	NP_006284.2	Q06418
TYRO3	NM_001330264.2 link	c.1127G>T	p.Gly376Val	missense_variant	Exon 10 of 19		NP_001317193.1	Q06418H0YNK6
TYRO3	XM_017022543.3 link	c.1262G>T	p.Gly421Val	missense_variant	Exon 10 of 19		XP_016878032.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TYRO3	ENST00000263798.8 link	c.1262G>T	p.Gly421Val	missense_variant	Exon 10 of 19	1	NM_006293.4	ENSP00000263798.3	Q06418
TYRO3	ENST00000559066.5 link	c.1127G>T	p.Gly376Val	missense_variant	Exon 10 of 19	5		ENSP00000454050.1	H0YNK6
TYRO3	ENST00000559815.1 link	n.313G>T		non_coding_transcript_exon_variant	Exon 3 of 4	5		ENSP00000453835.1	H0YN24

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1460488

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726534

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33444

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86168

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53318

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4746

European-Non Finnish (NFE)

AF:

0.00000450

AC:

AN:

1111986

Other (OTH)

AF:

0.00

AC:

AN:

60272

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

Feb 26, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.1262G>T (p.G421V) alteration is located in exon 10 (coding exon 10) of the TYRO3 gene. This alteration results from a G to T substitution at nucleotide position 1262, causing the glycine (G) at amino acid position 421 to be replaced by a valine (V). 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

0.084

BayesDel_addAF

Uncertain

0.012

BayesDel_noAF

Benign

-0.22

CADD

Benign

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.015

T;T

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.031

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.81

T;T

M_CAP

Benign

0.035

MetaRNN

Benign

0.11

T;T

MetaSVM

Benign

-0.84

MutationAssessor

Benign

0.76

.;N

PhyloP100

3.7

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-0.19

N;N

REVEL

Benign

0.19

Sift

Benign

0.62

T;T

Sift4G

Benign

0.29

T;T

Polyphen

0.21

.;B

Vest4

0.24

MVP

0.23

MPC

0.52

ClinPred

0.69

GERP RS

4.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.16

gMVP

0.47

Mutation Taster

=78/22

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over