rs438999
Positions:
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 1P and 16B. PP3BP6_Very_StrongBA1
The NM_006929.5(SKIC2):āc.452A>Gā(p.Gln151Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0997 in 1,611,646 control chromosomes in the GnomAD database, including 8,980 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.12 ( 1234 hom., cov: 32)
Exomes š: 0.098 ( 7746 hom. )
Consequence
SKIC2
NM_006929.5 missense
NM_006929.5 missense
Scores
2
15
Clinical Significance
Conservation
PhyloP100: 7.65
Genes affected
SKIC2 (HGNC:10898): (SKI2 subunit of superkiller complex) DEAD box proteins, characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD), are putative RNA helicases. They are implicated in a number of cellular processes involving alteration of RNA secondary structure such as translation initiation, nuclear and mitochondrial splicing, and ribosome and spliceosome assembly. Based on their distribution patterns, some members of this family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division. This gene encodes a DEAD box protein, which is a human homologue of yeast SKI2 and may be involved in antiviral activity by blocking translation of poly(A) deficient mRNAs. This gene is located in the class III region of the major histocompatibility complex. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
PP3
?
Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
BP6
?
Variant 6-31960529-A-G is Benign according to our data. Variant chr6-31960529-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 356316.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SKIC2 | NM_006929.5 | c.452A>G | p.Gln151Arg | missense_variant | 5/28 | ENST00000375394.7 | |
SKIC2 | XM_011514815.4 | c.452A>G | p.Gln151Arg | missense_variant | 5/25 | ||
SKIC2 | XM_047419259.1 | c.452A>G | p.Gln151Arg | missense_variant | 5/25 | ||
SKIC2 | XM_047419260.1 | c.452A>G | p.Gln151Arg | missense_variant | 5/24 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SKIC2 | ENST00000375394.7 | c.452A>G | p.Gln151Arg | missense_variant | 5/28 | 1 | NM_006929.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.118 AC: 17857AN: 151898Hom.: 1235 Cov.: 32
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GnomAD3 exomes AF: 0.0970 AC: 24386AN: 251370Hom.: 1423 AF XY: 0.0994 AC XY: 13512AN XY: 135892
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GnomAD4 exome AF: 0.0978 AC: 142765AN: 1459630Hom.: 7746 Cov.: 30 AF XY: 0.0986 AC XY: 71647AN XY: 726286
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GnomAD4 genome ? AF: 0.118 AC: 17879AN: 152016Hom.: 1234 Cov.: 32 AF XY: 0.115 AC XY: 8583AN XY: 74318
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Dec 03, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 29, 2016 | Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency - |
Trichohepatoenteric syndrome 2 Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Mar 06, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
P;P
PrimateAI
Benign
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
B
Vest4
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DG_spliceai
Position offset: 0
Find out detailed SpliceAI scores and Pangolin per-transcript scores at