15-73740251-C-T
Variant names:
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_001039614.3(INSYN1):c.548G>A(p.Arg183Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,613,876 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 30)
Exomes 𝑓: 0.0000027 ( 0 hom. )
Consequence
INSYN1
NM_001039614.3 missense
NM_001039614.3 missense
Scores
8
7
2
Clinical Significance
Conservation
PhyloP100: 7.29
Genes affected
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.815
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
INSYN1 | ENST00000569673.3 | c.548G>A | p.Arg183Gln | missense_variant | Exon 3 of 3 | 5 | NM_001039614.3 | ENSP00000457205.1 | ||
INSYN1 | ENST00000558834.1 | n.274G>A | non_coding_transcript_exon_variant | Exon 2 of 2 | 3 | |||||
INSYN1 | ENST00000559817.1 | c.*5G>A | downstream_gene_variant | 3 | ENSP00000452799.1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152180Hom.: 0 Cov.: 30
GnomAD3 genomes
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GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250660Hom.: 0 AF XY: 0.00000738 AC XY: 1AN XY: 135540
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GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461696Hom.: 0 Cov.: 35 AF XY: 0.00000550 AC XY: 4AN XY: 727182
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152180Hom.: 0 Cov.: 30 AF XY: 0.0000135 AC XY: 1AN XY: 74330
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
not provided Uncertain:1
Feb 08, 2023
Human Genome and Stem Cell Research Center, Department of Genetics and Evolutionary Biology, Institute of Biosciences, University of São Paulo
Significance: Uncertain significance
Review Status: no assertion criteria provided
Collection Method: research
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Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
T;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
.;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D
MetaSVM
Uncertain
D
PROVEAN
Uncertain
D;D
REVEL
Pathogenic
Sift
Pathogenic
D;D
Sift4G
Pathogenic
D;D
Polyphen
D;D
Vest4
MutPred
Loss of MoRF binding (P = 0.0285);Loss of MoRF binding (P = 0.0285);
MVP
MPC
ClinPred
D
GERP RS
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