14-57209770-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_006544.4(EXOC5):c.1735G>A(p.Val579Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Consequence
EXOC5
NM_006544.4 missense
NM_006544.4 missense
Scores
7
9
Clinical Significance
Conservation
PhyloP100: 7.76
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.36365628).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EXOC5 | NM_006544.4 | c.1735G>A | p.Val579Ile | missense_variant | 17/18 | ENST00000621441.5 | |
EXOC5 | XM_005267272.4 | c.1849G>A | p.Val617Ile | missense_variant | 17/18 | ||
EXOC5 | XM_047430882.1 | c.1570G>A | p.Val524Ile | missense_variant | 17/18 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EXOC5 | ENST00000621441.5 | c.1735G>A | p.Val579Ile | missense_variant | 17/18 | 1 | NM_006544.4 | P1 | |
EXOC5 | ENST00000554011.5 | n.1454G>A | non_coding_transcript_exon_variant | 7/8 | 1 | ||||
EXOC5 | ENST00000340918.11 | c.1540G>A | p.Val514Ile | missense_variant | 16/17 | 2 | |||
EXOC5 | ENST00000555148.5 | c.*1569G>A | 3_prime_UTR_variant, NMD_transcript_variant | 17/18 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD3 exomes AF: 0.00000414 AC: 1AN: 241362Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 130866
GnomAD3 exomes
AF:
AC:
1
AN:
241362
Hom.:
AF XY:
AC XY:
0
AN XY:
130866
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome Cov.: 30
GnomAD4 exome
Cov.:
30
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
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.1735G>A (p.V579I) alteration is located in exon 17 (coding exon 17) of the EXOC5 gene. This alteration results from a G to A substitution at nucleotide position 1735, causing the valine (V) at amino acid position 579 to be replaced by an isoleucine (I). 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
Pathogenic
Dann
Uncertain
DEOGEN2
Benign
T;T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
M;.;.
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
Sift4G
Uncertain
T;D;D
Polyphen
P;.;P
Vest4
MutPred
Gain of MoRF binding (P = 0.1405);.;.;
MVP
MPC
1.0
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