10-119902901-G-A
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_007190.4(SEC23IP):c.799G>A(p.Glu267Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000186 in 1,614,038 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 0.00026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00018 ( 0 hom. )
Consequence
SEC23IP
NM_007190.4 missense
NM_007190.4 missense
Scores
6
6
7
Clinical Significance
Conservation
PhyloP100: 9.35
Genes affected
SEC23IP (HGNC:17018): (SEC23 interacting protein) This gene encodes a member of the phosphatidic acid preferring-phospholipase A1 family. The encoded protein is localized to endoplasmic reticulum exit sites and plays a critical role in ER-Golgi transport as part of the multimeric coat protein II complex. An orthologous gene in frogs is required for normal neural crest cell development, suggesting that this gene may play a role in Waardenburg syndrome neural crest defects. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Feb 2011]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.034846008).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SEC23IP | NM_007190.4 | c.799G>A | p.Glu267Lys | missense_variant | 3/19 | ENST00000369075.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SEC23IP | ENST00000369075.8 | c.799G>A | p.Glu267Lys | missense_variant | 3/19 | 1 | NM_007190.4 | P4 | |
SEC23IP | ENST00000705471.1 | c.799G>A | p.Glu267Lys | missense_variant | 3/19 | A1 | |||
SEC23IP | ENST00000446561.1 | c.1G>A | p.Glu1Lys | missense_variant | 1/5 | 3 | |||
SEC23IP | ENST00000442952.1 | c.97G>A | p.Glu33Lys | missense_variant | 1/2 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.000256 AC: 39AN: 152174Hom.: 0 Cov.: 32
GnomAD3 genomes
?
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GnomAD3 exomes AF: 0.000354 AC: 89AN: 251482Hom.: 0 AF XY: 0.000368 AC XY: 50AN XY: 135914
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GnomAD4 exome AF: 0.000179 AC: 261AN: 1461864Hom.: 0 Cov.: 31 AF XY: 0.000188 AC XY: 137AN XY: 727238
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GnomAD4 genome ? AF: 0.000256 AC: 39AN: 152174Hom.: 0 Cov.: 32 AF XY: 0.000269 AC XY: 20AN XY: 74330
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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 | Jun 27, 2022 | The c.799G>A (p.E267K) alteration is located in exon 3 (coding exon 3) of the SEC23IP gene. This alteration results from a G to A substitution at nucleotide position 799, causing the glutamic acid (E) at amino acid position 267 to be replaced by a lysine (K). 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
Uncertain
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Pathogenic
DEOGEN2
Benign
T;T;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Pathogenic
M;.;.
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;.;N
REVEL
Uncertain
Sift
Uncertain
D;.;D
Sift4G
Uncertain
D;D;D
Polyphen
D;.;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
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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