chr18-736939-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PP3_Moderate
The NM_005433.4(YES1):c.1160T>C(p.Ile387Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,457,562 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.000010 ( 0 hom. )
Consequence
YES1
NM_005433.4 missense
NM_005433.4 missense
Scores
9
4
1
Clinical Significance
Conservation
PhyloP100: 9.11
Genes affected
YES1 (HGNC:12841): (YES proto-oncogene 1, Src family tyrosine kinase) This gene is the cellular homolog of the Yamaguchi sarcoma virus oncogene. The encoded protein has tyrosine kinase activity and belongs to the src family of proteins. This gene lies in close proximity to thymidylate synthase gene on chromosome 18, and a corresponding pseudogene has been found on chromosome 22. [provided by RefSeq, Jul 2008]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.928
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
YES1 | NM_005433.4 | c.1160T>C | p.Ile387Thr | missense_variant | 10/12 | ENST00000314574.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
YES1 | ENST00000314574.5 | c.1160T>C | p.Ile387Thr | missense_variant | 10/12 | 1 | NM_005433.4 | P1 | |
YES1 | ENST00000584307.5 | c.1160T>C | p.Ile387Thr | missense_variant | 10/12 | 1 | P1 | ||
ENST00000583314.1 | n.1194A>G | non_coding_transcript_exon_variant | 1/1 | ||||||
YES1 | ENST00000577961.5 | c.1175T>C | p.Ile392Thr | missense_variant | 10/12 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD3 exomes AF: 0.00000807 AC: 2AN: 247704Hom.: 0 AF XY: 0.0000149 AC XY: 2AN XY: 134202
GnomAD3 exomes
AF:
AC:
2
AN:
247704
Hom.:
AF XY:
AC XY:
2
AN XY:
134202
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000103 AC: 15AN: 1457562Hom.: 0 Cov.: 30 AF XY: 0.0000152 AC XY: 11AN XY: 725232
GnomAD4 exome
AF:
AC:
15
AN:
1457562
Hom.:
Cov.:
30
AF XY:
AC XY:
11
AN XY:
725232
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ExAC
?
AF:
AC:
1
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 | Dec 17, 2021 | The c.1160T>C (p.I387T) alteration is located in exon 10 (coding exon 9) of the YES1 gene. This alteration results from a T to C substitution at nucleotide position 1160, causing the isoleucine (I) at amino acid position 387 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;.;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Uncertain
D
MutationTaster
Benign
D;D;D
PrimateAI
Pathogenic
D
Sift4G
Pathogenic
D;D;D
Polyphen
0.99
.;D;D
Vest4
MutPred
0.71
.;Loss of stability (P = 0.1743);Loss of stability (P = 0.1743);
MVP
MPC
1.1
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at