rs11136254
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Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1
The NM_030974.4(SHARPIN):c.154C>A(p.Arg52=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.911 in 1,531,066 control chromosomes in the GnomAD database, including 637,285 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.86 ( 57704 hom., cov: 35)
Exomes 𝑓: 0.92 ( 579581 hom. )
Consequence
SHARPIN
NM_030974.4 synonymous
NM_030974.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.788
Genes affected
SHARPIN (HGNC:25321): (SHANK associated RH domain interactor) Enables polyubiquitin modification-dependent protein binding activity. Involved in protein linear polyubiquitination and regulation of signal transduction. Located in cytosol. Part of LUBAC complex. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.58).
BP6
?
Variant 8-144103600-G-T is Benign according to our data. Variant chr8-144103600-G-T is described in ClinVar as [Benign]. Clinvar id is 403434.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=0.788 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.974 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SHARPIN | NM_030974.4 | c.154C>A | p.Arg52= | synonymous_variant | 1/9 | ENST00000398712.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SHARPIN | ENST00000398712.7 | c.154C>A | p.Arg52= | synonymous_variant | 1/9 | 1 | NM_030974.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.865 AC: 131569AN: 152120Hom.: 57681 Cov.: 35
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GnomAD3 exomes AF: 0.927 AC: 117876AN: 127126Hom.: 54829 AF XY: 0.930 AC XY: 64811AN XY: 69688
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GnomAD4 exome AF: 0.916 AC: 1262982AN: 1378828Hom.: 579581 Cov.: 70 AF XY: 0.918 AC XY: 624457AN XY: 680092
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GnomAD4 genome ? AF: 0.865 AC: 131647AN: 152238Hom.: 57704 Cov.: 35 AF XY: 0.869 AC XY: 64655AN XY: 74438
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Benign:1
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 - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
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DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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