chr11-8937891-C-T
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_020646.3(ASCL3):c.271G>A(p.Gly91Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000725 in 1,614,078 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00034 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00076 ( 6 hom. )
Consequence
ASCL3
NM_020646.3 missense
NM_020646.3 missense
Scores
1
6
8
Clinical Significance
Conservation
PhyloP100: 5.04
Genes affected
ASCL3 (HGNC:740): (achaete-scute family bHLH transcription factor 3) Basic helix-loop-helix transcription factors, such as ASCL3, are essential for the determination of cell fate and the development and differentiation of numerous tissues (Jonsson et al., 2004 [PubMed 15475265]).[supplied by OMIM, Mar 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=0.10237336).
BS2
High Homozygotes in GnomAdExome4 at 6 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ASCL3 | NM_020646.3 | c.271G>A | p.Gly91Arg | missense_variant | 2/2 | ENST00000531618.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ASCL3 | ENST00000531618.2 | c.271G>A | p.Gly91Arg | missense_variant | 2/2 | NM_020646.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000342 AC: 52AN: 152096Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000298 AC: 75AN: 251280Hom.: 0 AF XY: 0.000294 AC XY: 40AN XY: 135852
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GnomAD4 exome AF: 0.000765 AC: 1118AN: 1461864Hom.: 6 Cov.: 42 AF XY: 0.000766 AC XY: 557AN XY: 727230
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GnomAD4 genome AF: 0.000342 AC: 52AN: 152214Hom.: 0 Cov.: 32 AF XY: 0.000376 AC XY: 28AN XY: 74418
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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 | Mar 29, 2022 | The c.271G>A (p.G91R) alteration is located in exon 2 (coding exon 1) of the ASCL3 gene. This alteration results from a G to A substitution at nucleotide position 271, causing the glycine (G) at amino acid position 91 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Benign
DANN
Pathogenic
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Benign
T
MetaSVM
Uncertain
D
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Uncertain
Sift
Benign
D
Sift4G
Benign
T
Vest4
MVP
ClinPred
T
GERP RS
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