15-41559319-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006293.4(TYRO3):​c.62C>T​(p.Pro21Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000407 in 491,696 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: not found (cov: 34)
Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

TYRO3
NM_006293.4 missense

Scores

3
1
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.173
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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.11624429).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TYRO3NM_006293.4 linkc.62C>T p.Pro21Leu missense_variant Exon 1 of 19 ENST00000263798.8 NP_006284.2 Q06418
TYRO3XM_017022543.3 linkc.62C>T p.Pro21Leu missense_variant Exon 1 of 19 XP_016878032.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TYRO3ENST00000263798.8 linkc.62C>T p.Pro21Leu missense_variant Exon 1 of 19 1 NM_006293.4 ENSP00000263798.3 Q06418
TYRO3ENST00000559066.5 linkc.-12+847C>T intron_variant Intron 1 of 18 5 ENSP00000454050.1 H0YNK6
TYRO3ENST00000560992.1 linkn.93C>T non_coding_transcript_exon_variant Exon 1 of 2 2

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD4 exome
AF:
0.00000407
AC:
2
AN:
491696
Hom.:
0
Cov.:
0
AF XY:
0.00000409
AC XY:
1
AN XY:
244674
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000557
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000448
GnomAD4 genome
Cov.:
34

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Feb 27, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.62C>T (p.P21L) alteration is located in exon 1 (coding exon 1) of the TYRO3 gene. This alteration results from a C to T substitution at nucleotide position 62, causing the proline (P) at amino acid position 21 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
0.14
BayesDel_addAF
Benign
-0.14
T
BayesDel_noAF
Benign
-0.44
CADD
Benign
11
DANN
Uncertain
0.99
DEOGEN2
Benign
0.11
T
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.061
N
LIST_S2
Benign
0.42
T
M_CAP
Pathogenic
0.59
D
MetaRNN
Benign
0.12
T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
-0.34
N
PrimateAI
Pathogenic
0.85
D
PROVEAN
Benign
-0.59
N
REVEL
Benign
0.14
Sift
Pathogenic
0.0
D
Sift4G
Benign
0.41
T
Polyphen
0.0
B
Vest4
0.16
MutPred
0.063
Loss of glycosylation at P21 (P = 0.0087);
MVP
0.068
MPC
0.40
ClinPred
0.25
T
GERP RS
2.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0
Varity_R
0.079
gMVP
0.35

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
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: rs17854578; hg19: chr15-41851517; API