14-57229823-T-C
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_006544.4(EXOC5):c.1207A>G(p.Ile403Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000654 in 1,376,262 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000065 ( 0 hom. )
Consequence
EXOC5
NM_006544.4 missense
NM_006544.4 missense
Scores
1
2
13
Clinical Significance
Conservation
PhyloP100: 6.22
Genes affected
EXOC5 (HGNC:10696): (exocyst complex component 5) 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 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. The complex is also essential for the biogenesis of epithelial cell surface polarity. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.19009307).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EXOC5 | NM_006544.4 | c.1207A>G | p.Ile403Val | missense_variant | 12/18 | ENST00000621441.5 | |
EXOC5 | XM_005267272.4 | c.1321A>G | p.Ile441Val | missense_variant | 12/18 | ||
EXOC5 | XM_047430882.1 | c.1042A>G | p.Ile348Val | missense_variant | 12/18 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EXOC5 | ENST00000621441.5 | c.1207A>G | p.Ile403Val | missense_variant | 12/18 | 1 | NM_006544.4 | P1 | |
EXOC5 | ENST00000554011.5 | n.926A>G | non_coding_transcript_exon_variant | 2/8 | 1 | ||||
EXOC5 | ENST00000340918.11 | c.1012A>G | p.Ile338Val | missense_variant | 11/17 | 2 | |||
EXOC5 | ENST00000555148.5 | c.*1041A>G | 3_prime_UTR_variant, NMD_transcript_variant | 12/18 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome AF: 0.00000654 AC: 9AN: 1376262Hom.: 0 Cov.: 27 AF XY: 0.0000103 AC XY: 7AN XY: 677646
GnomAD4 exome
AF:
AC:
9
AN:
1376262
Hom.:
Cov.:
27
AF XY:
AC XY:
7
AN XY:
677646
Gnomad4 AFR exome
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
Asia WGS
AF:
AC:
2
AN:
3478
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 14, 2023 | The c.1207A>G (p.I403V) alteration is located in exon 12 (coding exon 12) of the EXOC5 gene. This alteration results from a A to G substitution at nucleotide position 1207, causing the isoleucine (I) at amino acid position 403 to be replaced by a valine (V). 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
Benign
DEOGEN2
Benign
T;T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;.;.
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
Sift4G
Benign
T;T;T
Polyphen
B;.;B
Vest4
MutPred
Gain of disorder (P = 0.1088);Gain of disorder (P = 0.1088);.;
MVP
MPC
0.40
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at