3-10305108-G-T
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Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_183352.3(SEC13):c.633C>A(p.His211Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000558 in 1,613,994 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000055 ( 0 hom. )
Consequence
SEC13
NM_183352.3 missense
NM_183352.3 missense
Scores
13
3
3
Clinical Significance
Conservation
PhyloP100: 4.88
Genes affected
SEC13 (HGNC:10697): (SEC13 homolog, nuclear pore and COPII coat complex component) The protein encoded by this gene belongs to the SEC13 family of WD-repeat proteins. It is a constituent of the endoplasmic reticulum and the nuclear pore complex. It has similarity to the yeast SEC13 protein, which is required for vesicle biogenesis from endoplasmic reticulum during the transport of proteins. Multiple alternatively spliced transcript variants have been found. [provided by RefSeq, Oct 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.888
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SEC13 | NM_183352.3 | c.633C>A | p.His211Gln | missense_variant | 7/9 | ENST00000350697.8 | NP_899195.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SEC13 | ENST00000350697.8 | c.633C>A | p.His211Gln | missense_variant | 7/9 | 1 | NM_183352.3 | ENSP00000312122.4 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152206Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000239 AC: 6AN: 251058Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135660
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GnomAD4 exome AF: 0.00000547 AC: 8AN: 1461788Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4AN XY: 727202
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152206Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74358
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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 | Oct 03, 2023 | The c.633C>A (p.H211Q) alteration is located in exon 7 (coding exon 7) of the SEC13 gene. This alteration results from a C to A substitution at nucleotide position 633, causing the histidine (H) at amino acid position 211 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
.;.;T;.;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T;T;T;T;T
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
.;.;H;.;.
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;D;D;D;D
REVEL
Pathogenic
Sift
Pathogenic
D;D;D;D;D
Sift4G
Pathogenic
D;D;D;D;D
Polyphen
1.0
.;.;D;D;.
Vest4
MutPred
0.69
.;.;Gain of sheet (P = 0.0827);.;.;
MVP
MPC
0.85
ClinPred
D
GERP RS
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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