14-81486316-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.
The NM_005065.6(SEL1L):c.1771A>G(p.Ser591Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,614,066 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000011 ( 0 hom. )
Consequence
SEL1L
NM_005065.6 missense
NM_005065.6 missense
Scores
5
12
2
Clinical Significance
Conservation
PhyloP100: 7.66
Genes affected
SEL1L (HGNC:10717): (SEL1L adaptor subunit of SYVN1 ubiquitin ligase) The protein encoded by this gene is part of a protein complex required for the retrotranslocation or dislocation of misfolded proteins from the endoplasmic reticulum lumen to the cytosol, where they are degraded by the proteasome in a ubiquitin-dependent manner. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SEL1L | NM_005065.6 | c.1771A>G | p.Ser591Gly | missense_variant | 17/21 | ENST00000336735.9 | |
SEL1L | XM_005267988.4 | c.1708A>G | p.Ser570Gly | missense_variant | 17/21 | ||
SEL1L | XM_005267989.5 | c.1702A>G | p.Ser568Gly | missense_variant | 16/20 | ||
SEL1L | XM_047431676.1 | c.1639A>G | p.Ser547Gly | missense_variant | 16/20 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SEL1L | ENST00000336735.9 | c.1771A>G | p.Ser591Gly | missense_variant | 17/21 | 1 | NM_005065.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152220Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251378Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135846
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GnomAD4 exome AF: 0.0000109 AC: 16AN: 1461846Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 8AN XY: 727230
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GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152220Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74376
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 20, 2021 | The c.1771A>G (p.S591G) alteration is located in exon 1 (coding exon 1) of the SEL1L gene. This alteration results from a A to G substitution at nucleotide position 1771, causing the serine (S) at amino acid position 591 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Uncertain
T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D
M_CAP
Benign
D
MetaRNN
Uncertain
D
MetaSVM
Uncertain
T
MutationAssessor
Pathogenic
M
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D
REVEL
Uncertain
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MutPred
Loss of glycosylation at S591 (P = 0.0636);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
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