rs675117
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_007214.5(SEC63):c.564C>T(p.Asn188=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.857 in 1,605,432 control chromosomes in the GnomAD database, including 591,623 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.87 ( 57651 hom., cov: 33)
Exomes 𝑓: 0.86 ( 533972 hom. )
Consequence
SEC63
NM_007214.5 synonymous
NM_007214.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.536
Genes affected
SEC63 (HGNC:21082): (SEC63 homolog, protein translocation regulator) The Sec61 complex is the central component of the protein translocation apparatus of the endoplasmic reticulum (ER) membrane. The protein encoded by this gene and SEC62 protein are found to be associated with ribosome-free SEC61 complex. It is speculated that Sec61-Sec62-Sec63 may perform post-translational protein translocation into the ER. The Sec61-Sec62-Sec63 complex might also perform the backward transport of ER proteins that are subject to the ubiquitin-proteasome-dependent degradation pathway. The encoded protein is an integral membrane protein located in the rough ER. [provided by RefSeq, Jul 2008]
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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=-0.6).
BP6
?
Variant 6-107912725-G-A is Benign according to our data. Variant chr6-107912725-G-A is described in ClinVar as [Benign]. Clinvar id is 95474.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-107912725-G-A is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=0.536 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.897 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SEC63 | NM_007214.5 | c.564C>T | p.Asn188= | synonymous_variant | 6/21 | ENST00000369002.9 | |
SEC63 | XM_047418130.1 | c.396C>T | p.Asn132= | synonymous_variant | 6/21 | ||
SEC63 | XM_047418131.1 | c.144C>T | p.Asn48= | synonymous_variant | 5/20 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SEC63 | ENST00000369002.9 | c.564C>T | p.Asn188= | synonymous_variant | 6/21 | 1 | NM_007214.5 | P1 | |
SEC63 | ENST00000429168.1 | c.396C>T | p.Asn132= | synonymous_variant | 6/8 | 5 | |||
SEC63 | ENST00000484803.5 | n.486C>T | non_coding_transcript_exon_variant | 6/7 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.869 AC: 132207AN: 152148Hom.: 57605 Cov.: 33
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GnomAD3 exomes AF: 0.859 AC: 214598AN: 249874Hom.: 92420 AF XY: 0.859 AC XY: 116055AN XY: 135130
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GnomAD4 exome AF: 0.856 AC: 1243944AN: 1453166Hom.: 533972 Cov.: 32 AF XY: 0.857 AC XY: 619680AN XY: 723466
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GnomAD4 genome ? AF: 0.869 AC: 132311AN: 152266Hom.: 57651 Cov.: 33 AF XY: 0.867 AC XY: 64514AN XY: 74438
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ClinVar
Significance: Benign
Submissions summary: Benign:9
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:5
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jul 15, 2014 | - - |
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Polycystic liver disease 2 Benign:2
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 15, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 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:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 12, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
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