4-87047152-C-T
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2
The NM_001166693.3(AFF1):c.617C>T(p.Ser206Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Consequence
AFF1
NM_001166693.3 missense
NM_001166693.3 missense
Scores
13
6
Clinical Significance
Conservation
PhyloP100: 2.34
Genes affected
AFF1 (HGNC:7135): (ALF transcription elongation factor 1) This gene encodes a member of the AF4/ lymphoid nuclear protein related to the Fragile X E syndrome (FRAXE) family of proteins, which have been implicated in human childhood lymphoblastic leukemia, fragile chromosome X intellectual disability, and ataxia. It is the prevalent mixed-lineage leukemia fusion gene associated with spontaneous acute lymphoblastic leukemia. Members of this family have three conserved domains: an N-terminal homology domain, an AF4/ lymphoid nuclear protein domain, and a C-terminal homology domain. The protein functions as a regulator of RNA polymerase II-mediated transcription through elongation and chromatin remodeling functions. Through RNA interference screens, this gene has been shown to promote the expression of CD133, a plasma membrane glycoprotein required for leukemia cell survival. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2017]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM1
In a modified_residue Phosphoserine (size 0) in uniprot entity AFF1_HUMAN
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
AFF1 | NM_001166693.3 | c.617C>T | p.Ser206Phe | missense_variant | 4/21 | ENST00000395146.9 | NP_001160165.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
AFF1 | ENST00000395146.9 | c.617C>T | p.Ser206Phe | missense_variant | 4/21 | 2 | NM_001166693.3 | ENSP00000378578 | A2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 32
GnomAD4 exome
Cov.:
32
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
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 | Jan 09, 2024 | The c.617C>T (p.S206F) alteration is located in exon 4 (coding exon 3) of the AFF1 gene. This alteration results from a C to T substitution at nucleotide position 617, causing the serine (S) at amino acid position 206 to be replaced by a phenylalanine (F). 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
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
.;T;T;D;.
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D;D
M_CAP
Uncertain
D
MetaRNN
Uncertain
T;T;T;T;T
MetaSVM
Uncertain
T
MutationAssessor
Uncertain
.;.;.;M;.
MutationTaster
Benign
D;D;D
PrimateAI
Benign
T
PROVEAN
Uncertain
D;D;D;D;.
REVEL
Uncertain
Sift
Benign
D;D;D;T;.
Sift4G
Uncertain
D;D;D;D;D
Polyphen
1.0
.;.;.;D;.
Vest4
MutPred
0.45
.;.;.;Loss of phosphorylation at S199 (P = 0.007);Loss of phosphorylation at S199 (P = 0.007);
MVP
MPC
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
Publications
No publications associated with this variant yet.