18-747990-T-C
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_005433.4(YES1):c.400A>G(p.Ile134Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000161 in 1,613,840 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000016 ( 0 hom. )
Consequence
YES1
NM_005433.4 missense
NM_005433.4 missense
Scores
4
10
Clinical Significance
Conservation
PhyloP100: 3.87
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.19276658).
BS2
?
High AC in GnomAdExome at 5 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
YES1 | NM_005433.4 | c.400A>G | p.Ile134Val | missense_variant | 4/12 | ENST00000314574.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
YES1 | ENST00000314574.5 | c.400A>G | p.Ile134Val | missense_variant | 4/12 | 1 | NM_005433.4 | P1 | |
YES1 | ENST00000584307.5 | c.400A>G | p.Ile134Val | missense_variant | 4/12 | 1 | P1 | ||
YES1 | ENST00000577961.5 | c.415A>G | p.Ile139Val | missense_variant | 4/12 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152198Hom.: 0 Cov.: 32
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?
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GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251370Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135864
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GnomAD4 exome AF: 0.0000157 AC: 23AN: 1461642Hom.: 0 Cov.: 30 AF XY: 0.0000151 AC XY: 11AN XY: 727136
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GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152198Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74366
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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 | Nov 14, 2023 | The c.400A>G (p.I134V) alteration is located in exon 4 (coding exon 3) of the YES1 gene. This alteration results from a A to G substitution at nucleotide position 400, causing the isoleucine (I) at amino acid position 134 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;.;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
Sift4G
Benign
T;T;T
Polyphen
0.0090
.;B;B
Vest4
MutPred
0.46
.;Gain of ubiquitination at K138 (P = 0.0898);Gain of ubiquitination at K138 (P = 0.0898);
MVP
MPC
0.25
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at