rs7823
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_006308.3(HSPB3):āc.369T>Cā(p.Gly123Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.61 in 1,613,514 control chromosomes in the GnomAD database, including 303,229 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.63 ( 30948 hom., cov: 31)
Exomes š: 0.61 ( 272281 hom. )
Consequence
HSPB3
NM_006308.3 synonymous
NM_006308.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.12
Genes affected
HSPB3 (HGNC:5248): (heat shock protein family B (small) member 3) This gene encodes a muscle-specific small heat shock protein. A mutation in this gene is the cause of autosomal dominant distal hereditary motor neuropathy type 2C.[provided by RefSeq, Sep 2010]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.94).
BP6
Variant 5-54456158-T-C is Benign according to our data. Variant chr5-54456158-T-C is described in ClinVar as [Benign]. Clinvar id is 353903.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-54456158-T-C is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=-1.12 with no splicing effect.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.727 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
HSPB3 | NM_006308.3 | c.369T>C | p.Gly123Gly | synonymous_variant | 1/1 | ENST00000302005.3 | NP_006299.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
HSPB3 | ENST00000302005.3 | c.369T>C | p.Gly123Gly | synonymous_variant | 1/1 | 6 | NM_006308.3 | ENSP00000303394.1 |
Frequencies
GnomAD3 genomes AF: 0.631 AC: 95888AN: 151888Hom.: 30912 Cov.: 31
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GnomAD3 exomes AF: 0.585 AC: 147027AN: 251424Hom.: 44219 AF XY: 0.587 AC XY: 79801AN XY: 135886
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GnomAD4 exome AF: 0.607 AC: 887491AN: 1461508Hom.: 272281 Cov.: 49 AF XY: 0.606 AC XY: 440768AN XY: 727102
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GnomAD4 genome AF: 0.631 AC: 95978AN: 152006Hom.: 30948 Cov.: 31 AF XY: 0.626 AC XY: 46473AN XY: 74294
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ClinVar
Significance: Benign
Submissions summary: Benign:9
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Neuronopathy, distal hereditary motor, type 2C Benign:4
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Feb 01, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Aug 10, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 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:3
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Nov 16, 2017 | - - |
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
not specified Benign:2
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
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DANN
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Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at