4-55864363-A-G
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_001024924.2(EXOC1):āc.392A>Gā(p.Asn131Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000274 in 1,608,496 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 (ā ).
Frequency
Genomes: š 0.000039 ( 0 hom., cov: 32)
Exomes š: 0.000026 ( 0 hom. )
Consequence
EXOC1
NM_001024924.2 missense
NM_001024924.2 missense
Scores
9
9
Clinical Significance
Conservation
PhyloP100: 4.97
Genes affected
EXOC1 (HGNC:30380): (exocyst complex component 1) The protein encoded by this gene is a component of the exocyst complex, a multiple protein complex essential for targeting exocytic vesicles to specific docking sites on the plasma membrane. Though best characterized in yeast, the component proteins and functions of the exocyst complex have been demonstrated to be highly conserved in higher eukaryotes. At least eight components of the exocyst complex, including this protein, are found to interact with the actin cytoskeletal remodeling and vesicle transport machinery. Alternatively spliced transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Jul 2008]
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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=0.04670894).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EXOC1 | NM_001024924.2 | c.392A>G | p.Asn131Ser | missense_variant | 4/19 | ENST00000381295.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EXOC1 | ENST00000381295.7 | c.392A>G | p.Asn131Ser | missense_variant | 4/19 | 1 | NM_001024924.2 | A1 | |
EXOC1 | ENST00000346134.11 | c.392A>G | p.Asn131Ser | missense_variant | 4/19 | 2 | A1 | ||
EXOC1 | ENST00000349598.6 | c.392A>G | p.Asn131Ser | missense_variant | 4/18 | 2 | P3 | ||
EXOC1 | ENST00000505501.1 | n.377A>G | non_coding_transcript_exon_variant | 3/4 | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152262Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000565 AC: 14AN: 248006Hom.: 0 AF XY: 0.0000373 AC XY: 5AN XY: 133974
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GnomAD4 exome AF: 0.0000261 AC: 38AN: 1456116Hom.: 0 Cov.: 30 AF XY: 0.0000290 AC XY: 21AN XY: 723854
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GnomAD4 genome AF: 0.0000394 AC: 6AN: 152380Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74518
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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 | Feb 06, 2023 | The c.392A>G (p.N131S) alteration is located in exon 4 (coding exon 3) of the EXOC1 gene. This alteration results from a A to G substitution at nucleotide position 392, causing the asparagine (N) at amino acid position 131 to be replaced by a serine (S). 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
Uncertain
T;T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L;L
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D
REVEL
Benign
Sift
Uncertain
D;D;D
Sift4G
Uncertain
D;D;D
Polyphen
B;B;D
Vest4
MVP
MPC
ClinPred
T
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