6-107921806-G-GT
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_007214.5(SEC63):c.442_443insA(p.Ala148AspfsTer8) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 31)
Consequence
SEC63
NM_007214.5 frameshift
NM_007214.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 7.23
Publications
0 publications found
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]
SEC63 Gene-Disease associations (from GenCC):
- polycystic liver disease 2Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), ClinGen
- polycystic liver disease 1Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 11 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 6-107921806-G-GT is Pathogenic according to our data. Variant chr6-107921806-G-GT is described in ClinVar as [Pathogenic]. Clinvar id is 2168.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SEC63 | NM_007214.5 | c.442_443insA | p.Ala148AspfsTer8 | frameshift_variant | Exon 4 of 21 | ENST00000369002.9 | NP_009145.1 | |
SEC63 | XM_047418130.1 | c.274_275insA | p.Ala92AspfsTer8 | frameshift_variant | Exon 4 of 21 | XP_047274086.1 | ||
SEC63 | XM_047418131.1 | c.22_23insA | p.Ala8AspfsTer8 | frameshift_variant | Exon 3 of 20 | XP_047274087.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SEC63 | ENST00000369002.9 | c.442_443insA | p.Ala148AspfsTer8 | frameshift_variant | Exon 4 of 21 | 1 | NM_007214.5 | ENSP00000357998.4 | ||
SEC63 | ENST00000429168.1 | c.274_275insA | p.Ala92AspfsTer8 | frameshift_variant | Exon 4 of 8 | 5 | ENSP00000403144.1 | |||
SEC63 | ENST00000484803.5 | n.364_365insA | non_coding_transcript_exon_variant | Exon 4 of 7 | 2 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD3 genomes
Cov.:
31
GnomAD4 exome Cov.: 28
GnomAD4 exome
Cov.:
28
GnomAD4 genome Cov.: 31
GnomAD4 genome
Cov.:
31
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Polycystic liver disease 2 Pathogenic:1
Jun 01, 2004
OMIM
Significance:Pathogenic
Review Status:no assertion criteria provided
Collection Method:literature only
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Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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