Variant 15-41570036-G-T 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.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. 14/21 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

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=0.11064789).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TYRO3	NM_006293.4 linkuse as main transcript	c.1262G>T	p.Gly421Val	missense_variant	10/19	ENST00000263798.8	NP_006284.2
TYRO3	NM_001330264.2 linkuse as main transcript	c.1127G>T	p.Gly376Val	missense_variant	10/19		NP_001317193.1
TYRO3	XM_017022543.3 linkuse as main transcript	c.1262G>T	p.Gly421Val	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.1262G>T	p.Gly421Val	missense_variant	10/19	1	NM_006293.4	ENSP00000263798	A2
TYRO3	ENST00000559066.5 linkuse as main transcript	c.1127G>T	p.Gly376Val	missense_variant	10/19	5		ENSP00000454050	P4
TYRO3	ENST00000559815.1 linkuse as main transcript	c.316G>T	p.Ala106Ser	missense_variant, NMD_transcript_variant	3/4	5		ENSP00000453835

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

Gnomad4 AFR exome

AF:

0.00

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:

0.00000450

Gnomad4 OTH exome

AF:

0.00

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

Feb 26, 2024

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

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

MutationTaster

Benign

1.0

D;D

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

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

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