15-41561570-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006293.4(TYRO3):​c.340C>T​(p.Arg114Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000163 in 1,593,770 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 34)
Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

TYRO3
NM_006293.4 missense

Scores

8
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.39
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TYRO3NM_006293.4 linkc.340C>T p.Arg114Trp missense_variant Exon 3 of 19 ENST00000263798.8 NP_006284.2 Q06418
TYRO3NM_001330264.2 linkc.205C>T p.Arg69Trp missense_variant Exon 3 of 19 NP_001317193.1 Q06418H0YNK6
TYRO3XM_017022543.3 linkc.340C>T p.Arg114Trp missense_variant Exon 3 of 19 XP_016878032.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TYRO3ENST00000263798.8 linkc.340C>T p.Arg114Trp missense_variant Exon 3 of 19 1 NM_006293.4 ENSP00000263798.3 Q06418
TYRO3ENST00000559066.5 linkc.205C>T p.Arg69Trp missense_variant Exon 3 of 19 5 ENSP00000454050.1 H0YNK6
TYRO3ENST00000560992.1 linkn.599C>T non_coding_transcript_exon_variant Exon 2 of 2 2

Frequencies

GnomAD3 genomes
AF:
0.0000394
AC:
6
AN:
152232
Hom.:
0
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.000121
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000138
AC:
3
AN:
217134
Hom.:
0
AF XY:
0.00000854
AC XY:
1
AN XY:
117070
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000650
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000202
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000139
AC:
20
AN:
1441538
Hom.:
0
Cov.:
33
AF XY:
0.0000126
AC XY:
9
AN XY:
715142
show subpopulations
Gnomad4 AFR exome
AF:
0.0000605
Gnomad4 AMR exome
AF:
0.0000246
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000130
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000997
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000394
AC:
6
AN:
152232
Hom.:
0
Cov.:
34
AF XY:
0.0000538
AC XY:
4
AN XY:
74378
show subpopulations
Gnomad4 AFR
AF:
0.000121
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000565
Hom.:
0
Bravo
AF:
0.00000756

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 20, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.340C>T (p.R114W) alteration is located in exon 3 (coding exon 3) of the TYRO3 gene. This alteration results from a C to T substitution at nucleotide position 340, causing the arginine (R) at amino acid position 114 to be replaced by a tryptophan (W). 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
0.085
BayesDel_addAF
Benign
-0.050
T
BayesDel_noAF
Benign
-0.31
CADD
Benign
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.029
T;T
Eigen
Uncertain
0.42
Eigen_PC
Uncertain
0.39
FATHMM_MKL
Uncertain
0.78
D
LIST_S2
Uncertain
0.87
D;D
M_CAP
Benign
0.079
D
MetaRNN
Uncertain
0.57
D;D
MetaSVM
Benign
-0.36
T
MutationAssessor
Benign
1.8
.;L
PrimateAI
Benign
0.25
T
PROVEAN
Benign
-2.1
N;N
REVEL
Uncertain
0.33
Sift
Benign
0.12
T;T
Sift4G
Uncertain
0.034
D;D
Polyphen
1.0
.;D
Vest4
0.41
MutPred
0.58
.;Loss of disorder (P = 0.0337);
MVP
0.30
MPC
1.1
ClinPred
0.88
D
GERP RS
4.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0
Varity_R
0.25
gMVP
0.53

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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.

Other links and lift over

dbSNP: rs1267379170; hg19: chr15-41853768; COSMIC: COSV99778362; COSMIC: COSV99778362; API