chr21-43104346-G-A
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM1PM5PP2PP3_ModeratePP5
The NM_006758.3(U2AF1):c.101C>T(p.Ser34Phe) variant causes a missense change involving the alteration of a conserved nucleotide. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S34Y) has been classified as Likely pathogenic.
Frequency
Genomes: 𝑓 0.0 ( 0 hom., cov: 0)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
U2AF1
NM_006758.3 missense
NM_006758.3 missense
Scores
14
3
1
Clinical Significance
Conservation
PhyloP100: 9.05
Genes affected
U2AF1 (HGNC:12453): (U2 small nuclear RNA auxiliary factor 1) This gene belongs to the splicing factor SR family of genes. U2 auxiliary factor, comprising a large and a small subunit, is a non-snRNP protein required for the binding of U2 snRNP to the pre-mRNA branch site. This gene encodes the small subunit which plays a critical role in both constitutive and enhancer-dependent RNA splicing by directly mediating interactions between the large subunit and proteins bound to the enhancers. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
PM1
?
In a chain Splicing factor U2AF 35 kDa subunit (size 238) in uniprot entity U2AF1_HUMAN there are 4 pathogenic changes around while only 0 benign (100%) in NM_006758.3
PM5
?
Other missense variant is known to change same aminoacid residue: Variant chr21-43104346-G-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 376026.Status of the report is no_assertion_criteria_provided, 0 stars.
PP2
?
Missense variant where missense usually causes diseases, U2AF1
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.875
PP5
?
Variant 21-43104346-G-A is Pathogenic according to our data. Variant chr21-43104346-G-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 376025.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
U2AF1 | NM_006758.3 | c.101C>T | p.Ser34Phe | missense_variant | 2/8 | ENST00000291552.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
U2AF1 | ENST00000291552.9 | c.101C>T | p.Ser34Phe | missense_variant | 2/8 | 1 | NM_006758.3 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.00 AC: 0AN: 986Hom.: 0 Cov.: 0 FAILED QC
GnomAD3 genomes
?
AF:
AC:
0
AN:
986
Hom.:
Cov.:
0
FAILED QC
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 17950Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0AN XY: 9092
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
17950
Hom.:
Cov.:
0
AF XY:
AC XY:
0
AN XY:
9092
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 ? Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0AN: 986Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0AN XY: 500
GnomAD4 genome
?
Data not reliable, filtered out with message: AC0;AS_VQSR
AF:
AC:
0
AN:
986
Hom.:
Cov.:
0
AF XY:
AC XY:
0
AN XY:
500
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
ESP6500AA
AF:
AC:
1
ESP6500EA
AF:
AC:
0
ExAC
?
AF:
AC:
5
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:9
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Myelodysplastic syndrome Pathogenic:1
Likely pathogenic, no assertion criteria provided | literature only | Database of Curated Mutations (DoCM) | May 31, 2016 | - - |
Malignant neoplasm of body of uterus Pathogenic:1
Likely pathogenic, no assertion criteria provided | literature only | Database of Curated Mutations (DoCM) | May 31, 2016 | - - |
Pancreatic adenocarcinoma Pathogenic:1
Likely pathogenic, no assertion criteria provided | literature only | Database of Curated Mutations (DoCM) | May 31, 2016 | - - |
Lung adenocarcinoma Pathogenic:1
Likely pathogenic, no assertion criteria provided | literature only | Database of Curated Mutations (DoCM) | May 31, 2016 | - - |
Neoplasm of uterine cervix Pathogenic:1
Likely pathogenic, no assertion criteria provided | literature only | Database of Curated Mutations (DoCM) | May 31, 2016 | - - |
Transitional cell carcinoma of the bladder Pathogenic:1
Likely pathogenic, no assertion criteria provided | literature only | Database of Curated Mutations (DoCM) | May 31, 2016 | - - |
Uterine carcinosarcoma Pathogenic:1
Likely pathogenic, no assertion criteria provided | literature only | Database of Curated Mutations (DoCM) | May 31, 2016 | - - |
Squamous cell carcinoma of the head and neck Pathogenic:1
Likely pathogenic, no assertion criteria provided | literature only | Database of Curated Mutations (DoCM) | May 31, 2016 | - - |
Acute myeloid leukemia Pathogenic:1
Likely pathogenic, no assertion criteria provided | literature only | Database of Curated Mutations (DoCM) | May 31, 2016 | - - |
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
Pathogenic
D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
H;H
MutationTaster
Benign
D;D;D;D;D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;D
REVEL
Pathogenic
Sift
Pathogenic
D;D
Sift4G
Pathogenic
D;D
Polyphen
1.0
.;D
Vest4
MVP
MPC
2.7
ClinPred
D
GERP RS
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