1-185300077-C-T
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PP2PP3BS2
The NM_006469.5(IVNS1ABP):c.1423G>A(p.Gly475Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000229 in 1,613,246 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 (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000023 ( 0 hom. )
Consequence
IVNS1ABP
NM_006469.5 missense
NM_006469.5 missense
Scores
9
8
2
Clinical Significance
Conservation
PhyloP100: 7.51
Genes affected
IVNS1ABP (HGNC:16951): (influenza virus NS1A binding protein) Involved in RNA splicing; negative regulation of protein ubiquitination; and response to virus. Located in cytosol. Implicated in immunodeficiency 70. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PP2
Missense variant where missense usually causes diseases, IVNS1ABP
PP3
MetaRNN computational evidence supports a deleterious effect, 0.806
BS2
High AC in GnomAdExome4 at 34 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IVNS1ABP | NM_006469.5 | c.1423G>A | p.Gly475Ser | missense_variant | 13/15 | ENST00000367498.8 | |
IVNS1ABP | XM_047434070.1 | c.1423G>A | p.Gly475Ser | missense_variant | 13/15 | ||
IVNS1ABP | XM_047434096.1 | c.1156G>A | p.Gly386Ser | missense_variant | 12/14 | ||
IVNS1ABP | XM_047434109.1 | c.769G>A | p.Gly257Ser | missense_variant | 7/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IVNS1ABP | ENST00000367498.8 | c.1423G>A | p.Gly475Ser | missense_variant | 13/15 | 1 | NM_006469.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152070Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000399 AC: 10AN: 250730Hom.: 0 AF XY: 0.0000443 AC XY: 6AN XY: 135534
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GnomAD4 exome AF: 0.0000233 AC: 34AN: 1461176Hom.: 0 Cov.: 33 AF XY: 0.0000303 AC XY: 22AN XY: 726932
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GnomAD4 genome AF: 0.0000197 AC: 3AN: 152070Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74268
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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 | Feb 27, 2024 | The c.1423G>A (p.G475S) alteration is located in exon 13 (coding exon 11) of the IVNS1ABP gene. This alteration results from a G to A substitution at nucleotide position 1423, causing the glycine (G) at amino acid position 475 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
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
D
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Benign
D
MetaRNN
Pathogenic
D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D
REVEL
Uncertain
Sift
Pathogenic
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MVP
MPC
ClinPred
D
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