Variant 15-41567406-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_006293.4(TYRO3):c.830C>T(p.Pro277Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000357 in 1,606,042 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: 𝑓 0.00038 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00035 ( 0 hom. )

Consequence

TYRO3
NM_006293.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.92

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.030841798).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TYRO3	NM_006293.4 linkuse as main transcript	c.830C>T	p.Pro277Leu	missense_variant	7/19	ENST00000263798.8	NP_006284.2
TYRO3	NM_001330264.2 linkuse as main transcript	c.695C>T	p.Pro232Leu	missense_variant	7/19		NP_001317193.1
TYRO3	XM_017022543.3 linkuse as main transcript	c.830C>T	p.Pro277Leu	missense_variant	7/19		XP_016878032.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
TYRO3	ENST00000263798.8 linkuse as main transcript	c.830C>T	p.Pro277Leu	missense_variant	7/19	1	NM_006293.4	ENSP00000263798	A2
TYRO3	ENST00000559066.5 linkuse as main transcript	c.695C>T	p.Pro232Leu	missense_variant	7/19	5		ENSP00000454050	P4
TYRO3	ENST00000560227.1 linkuse as main transcript	n.405C>T		non_coding_transcript_exon_variant	2/3	5
TYRO3	ENST00000559815.1 linkuse as main transcript	c.29C>T	p.Pro10Leu	missense_variant, NMD_transcript_variant	1/4	5		ENSP00000453835

Frequencies

GnomAD3 genomes

AF:

0.000381

AC:

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00111

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:

0.000558

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000333

AC:

AN:

243562

Hom.:

AF XY:

0.000334

AC XY:

AN XY:

131654

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000961

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:

0.000370

Gnomad OTH exome

AF:

0.00135

GnomAD4 exome

AF:

0.000354

AC:

515

AN:

1453690

Hom.:

Cov.:

AF XY:

0.000371

AC XY:

268

AN XY:

723022

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000914

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000189

Gnomad4 NFE exome

AF:

0.000406

Gnomad4 OTH exome

AF:

0.000367

GnomAD4 genome

AF:

0.000381

AC:

AN:

152352

Hom.:

Cov.:

AF XY:

0.000443

AC XY:

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.00111

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000559

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000325

Hom.:

Bravo

AF:

0.000521

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000814

AC:

ExAC

AF:

0.000296

AC:

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

Sep 01, 2021

The c.830C>T (p.P277L) alteration is located in exon 7 (coding exon 7) of the TYRO3 gene. This alteration results from a C to T substitution at nucleotide position 830, causing the proline (P) at amino acid position 277 to be replaced by a leucine (L). 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

0.093

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.027

T;T

Eigen

Benign

-0.037

Eigen_PC

Benign

0.13

FATHMM_MKL

Uncertain

0.76

LIST_S2

Benign

0.65

T;T

M_CAP

Benign

0.0093

MetaRNN

Benign

0.031

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.77

.;N

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-1.8

N;N

REVEL

Benign

0.076

Sift

Benign

0.053

T;T

Sift4G

Benign

0.33

T;T

Polyphen

0.0010

.;B

Vest4

0.38

MVP

0.082

MPC

0.41

ClinPred

0.037

GERP RS

4.6

Varity_R

0.11

gMVP

0.59

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

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