1-47219791-C-A
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_001290403.2(TAL1):c.925G>T(p.Ala309Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000473 in 1,611,664 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00027 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00049 ( 1 hom. )
Consequence
TAL1
NM_001290403.2 missense
NM_001290403.2 missense
Scores
3
15
Clinical Significance
Conservation
PhyloP100: 2.31
Genes affected
TAL1 (HGNC:11556): (TAL bHLH transcription factor 1, erythroid differentiation factor) Enables several functions, including DNA-binding transcription factor activity; E-box binding activity; and histone deacetylase binding activity. Involved in several processes, including myeloid cell differentiation; positive regulation of cellular component organization; and positive regulation of erythrocyte differentiation. Located in chromatin and nucleoplasm. Part of transcription regulator complex. Implicated in acute lymphoblastic leukemia. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.036818624).
BS2
?
High AC in GnomAd at 41 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TAL1 | NM_001290403.2 | c.925G>T | p.Ala309Ser | missense_variant | 5/5 | ENST00000691006.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TAL1 | ENST00000691006.1 | c.925G>T | p.Ala309Ser | missense_variant | 5/5 | NM_001290403.2 | P1 | ||
TAL1 | ENST00000294339.3 | c.925G>T | p.Ala309Ser | missense_variant | 4/4 | 1 | P1 | ||
TAL1 | ENST00000371884.6 | c.925G>T | p.Ala309Ser | missense_variant | 5/5 | 1 | P1 | ||
TAL1 | ENST00000459729.1 | n.693G>T | non_coding_transcript_exon_variant | 3/3 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.000269 AC: 41AN: 152192Hom.: 0 Cov.: 32
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?
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GnomAD3 exomes AF: 0.000411 AC: 100AN: 243590Hom.: 0 AF XY: 0.000390 AC XY: 52AN XY: 133194
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GnomAD4 exome AF: 0.000494 AC: 721AN: 1459472Hom.: 1 Cov.: 29 AF XY: 0.000475 AC XY: 345AN XY: 726096
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GnomAD4 genome ? AF: 0.000269 AC: 41AN: 152192Hom.: 0 Cov.: 32 AF XY: 0.000296 AC XY: 22AN XY: 74344
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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 | May 11, 2022 | The c.925G>T (p.A309S) alteration is located in exon 4 (coding exon 3) of the TAL1 gene. This alteration results from a G to T substitution at nucleotide position 925, causing the alanine (A) at amino acid position 309 to be replaced by a serine (S). 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
Benign
DEOGEN2
Benign
T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Benign
T;T
MetaSVM
Uncertain
T
MutationAssessor
Benign
N;N
MutationTaster
Benign
N;N;N
PrimateAI
Benign
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
B;B
Vest4
MVP
MPC
0.62
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