chr9-136446907-C-T
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong
The NM_014866.2(SEC16A):c.6740G>A(p.Gly2247Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000961 in 1,613,458 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000099 ( 1 hom., cov: 32)
Exomes 𝑓: 0.000096 ( 1 hom. )
Consequence
SEC16A
NM_014866.2 missense
NM_014866.2 missense
Scores
4
14
Clinical Significance
Conservation
PhyloP100: 1.26
Genes affected
SEC16A (HGNC:29006): (SEC16 homolog A, endoplasmic reticulum export factor) This gene encodes a protein that forms part of the Sec16 complex. This protein has a role in protein transport from the endoplasmic reticulum (ER) to the Golgi and mediates COPII vesicle formation at the transitional ER. Alternative splicing results in multiple transcript variants that encode different protein isoforms. [provided by RefSeq, Feb 2013]
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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 (MetaRNN=0.019035041).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SEC16A | NM_014866.2 | c.6740G>A | p.Gly2247Glu | missense_variant | 28/32 | ENST00000684901.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SEC16A | ENST00000684901.1 | c.6740G>A | p.Gly2247Glu | missense_variant | 28/32 | NM_014866.2 | A2 |
Frequencies
GnomAD3 genomes AF: 0.0000986 AC: 15AN: 152140Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.0000885 AC: 22AN: 248622Hom.: 0 AF XY: 0.000111 AC XY: 15AN XY: 134940
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GnomAD4 exome AF: 0.0000958 AC: 140AN: 1461200Hom.: 1 Cov.: 32 AF XY: 0.0000880 AC XY: 64AN XY: 726888
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GnomAD4 genome AF: 0.0000985 AC: 15AN: 152258Hom.: 1 Cov.: 32 AF XY: 0.000148 AC XY: 11AN XY: 74450
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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 | Nov 17, 2023 | The c.6740G>A (p.G2247E) alteration is located in exon 28 (coding exon 26) of the SEC16A gene. This alteration results from a G to A substitution at nucleotide position 6740, causing the glycine (G) at amino acid position 2247 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
.;T;T;T;.;T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T;T;T;T;T;T
M_CAP
Uncertain
D
MetaRNN
Benign
T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
N;N;N;N;N;N
PrimateAI
Uncertain
T
PROVEAN
Benign
N;.;N;N;N;D;N
REVEL
Benign
Sift
Uncertain
D;.;D;T;T;D;D
Sift4G
Benign
T;T;T;T;T;T;T
Polyphen
0.24, 0.99
.;B;.;.;.;D;.
Vest4
MutPred
0.23
.;.;.;.;Gain of helix (P = 0.0496);.;Gain of helix (P = 0.0496);
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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