chr3-128055506-C-G
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong
The NM_013336.4(SEC61A1):c.76-10C>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 1,451,362 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: not found (cov: 33)
Exomes 𝑓: 0.000013 ( 0 hom. )
Consequence
SEC61A1
NM_013336.4 splice_polypyrimidine_tract, intron
NM_013336.4 splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.0004248
2
Clinical Significance
Conservation
PhyloP100: -0.188
Genes affected
SEC61A1 (HGNC:18276): (SEC61 translocon subunit alpha 1) The protein encoded by this gene belongs to the SECY/SEC61- alpha family. It appears to play a crucial role in the insertion of secretory and membrane polypeptides into the endoplasmic reticulum. This protein found to be tightly associated with membrane-bound ribosomes, either directly or through adaptor proteins. This gene encodes an alpha subunit of the heteromeric SEC61 complex, which also contains beta and gamma subunits. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SEC61A1 | NM_013336.4 | c.76-10C>G | splice_polypyrimidine_tract_variant, intron_variant | ENST00000243253.8 | |||
SEC61A1 | NM_001400328.1 | c.94-10C>G | splice_polypyrimidine_tract_variant, intron_variant | ||||
SEC61A1 | NM_001400329.1 | c.-84-10C>G | splice_polypyrimidine_tract_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SEC61A1 | ENST00000243253.8 | c.76-10C>G | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_013336.4 | P4 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251468Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135904
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GnomAD4 exome AF: 0.0000131 AC: 19AN: 1451362Hom.: 0 Cov.: 30 AF XY: 0.0000111 AC XY: 8AN XY: 722760
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GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 10, 2021 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has not been reported in the literature in individuals with SEC61A1-related conditions. This variant is present in population databases (rs770594530, ExAC 0.01%). This sequence change falls in intron 2 of the SEC61A1 gene. It does not directly change the encoded amino acid sequence of the SEC61A1 protein. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at