Variant 15-41570080-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.1306G>A(p.Val436Met) 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

TYRO3
NM_006293.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.06

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=0.25270563).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TYRO3	NM_006293.4 linkuse as main transcript	c.1306G>A	p.Val436Met	missense_variant	10/19	ENST00000263798.8	NP_006284.2
TYRO3	NM_001330264.2 linkuse as main transcript	c.1171G>A	p.Val391Met	missense_variant	10/19		NP_001317193.1
TYRO3	XM_017022543.3 linkuse as main transcript	c.1306G>A	p.Val436Met	missense_variant	10/19		XP_016878032.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
TYRO3	ENST00000263798.8 linkuse as main transcript	c.1306G>A	p.Val436Met	missense_variant	10/19	1	NM_006293.4	ENSP00000263798	A2
TYRO3	ENST00000559066.5 linkuse as main transcript	c.1171G>A	p.Val391Met	missense_variant	10/19	5		ENSP00000454050	P4
TYRO3	ENST00000559815.1 linkuse as main transcript	c.360G>A	p.Val120=	synonymous_variant, NMD_transcript_variant	3/4	5		ENSP00000453835

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 20, 2024

The c.1306G>A (p.V436M) alteration is located in exon 10 (coding exon 10) of the TYRO3 gene. This alteration results from a G to A substitution at nucleotide position 1306, causing the valine (V) at amino acid position 436 to be replaced by a methionine (M). 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

0.16

BayesDel_addAF

Benign

-0.030

BayesDel_noAF

Benign

-0.28

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.030

T;T

Eigen

Uncertain

0.36

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Uncertain

0.83

LIST_S2

Uncertain

0.93

D;D

M_CAP

Benign

0.033

MetaRNN

Benign

0.25

T;T

MetaSVM

Benign

-0.47

MutationAssessor

Benign

1.8

.;L

MutationTaster

Benign

0.93

D;D

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-0.90

N;N

REVEL

Uncertain

0.30

Sift

Uncertain

0.027

D;D

Sift4G

Uncertain

0.030

D;D

Polyphen

0.98

.;D

Vest4

0.43

MutPred

0.47

.;Gain of sheet (P = 0.1208);

MVP

0.40

MPC

1.0

ClinPred

0.69

GERP RS

4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.073

gMVP

0.24

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over