chr6-107867756-T-A
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Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBS1_SupportingBS2
The NM_007214.5(SEC63):c.*3948A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00343 in 134,170 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0034 ( 0 hom., cov: 32)
Failed GnomAD Quality Control
Consequence
SEC63
NM_007214.5 3_prime_UTR
NM_007214.5 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0380
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 -9 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00343 (460/134170) while in subpopulation NFE AF= 0.00558 (346/62030). AF 95% confidence interval is 0.00509. There are 0 homozygotes in gnomad4. There are 211 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
BS2
High AC in GnomAd4 at 460 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SEC63 | NM_007214.5 | c.*3948A>T | 3_prime_UTR_variant | 21/21 | ENST00000369002.9 | ||
SEC63 | XM_047418130.1 | c.*3948A>T | 3_prime_UTR_variant | 21/21 | |||
SEC63 | XM_047418131.1 | c.*3948A>T | 3_prime_UTR_variant | 20/20 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SEC63 | ENST00000369002.9 | c.*3948A>T | 3_prime_UTR_variant | 21/21 | 1 | NM_007214.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00344 AC: 461AN: 134088Hom.: 0 Cov.: 32
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GnomAD4 exome Data not reliable, filtered out with message: AC0AC: 0AN: 0Hom.: 0 Cov.: 0AC XY: 0AN XY: 0
GnomAD4 exome
Data not reliable, filtered out with message: AC0
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GnomAD4 genome AF: 0.00343 AC: 460AN: 134170Hom.: 0 Cov.: 32 AF XY: 0.00325 AC XY: 211AN XY: 64974
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Polycystic liver disease 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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