chr14-57210005-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_006544.4(EXOC5):c.1670A>G(p.Lys557Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000691 in 1,446,998 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )
Consequence
EXOC5
NM_006544.4 missense
NM_006544.4 missense
Scores
2
7
7
Clinical Significance
Conservation
PhyloP100: 7.90
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 Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EXOC5 | NM_006544.4 | c.1670A>G | p.Lys557Arg | missense_variant | 16/18 | ENST00000621441.5 | |
EXOC5 | XM_005267272.4 | c.1784A>G | p.Lys595Arg | missense_variant | 16/18 | ||
EXOC5 | XM_047430882.1 | c.1505A>G | p.Lys502Arg | missense_variant | 16/18 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EXOC5 | ENST00000621441.5 | c.1670A>G | p.Lys557Arg | missense_variant | 16/18 | 1 | NM_006544.4 | P1 | |
EXOC5 | ENST00000554011.5 | n.1389A>G | non_coding_transcript_exon_variant | 6/8 | 1 | ||||
EXOC5 | ENST00000340918.11 | c.1475A>G | p.Lys492Arg | missense_variant | 15/17 | 2 | |||
EXOC5 | ENST00000555148.5 | c.*1504A>G | 3_prime_UTR_variant, NMD_transcript_variant | 16/18 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome AF: 6.91e-7 AC: 1AN: 1446998Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0AN XY: 719760
GnomAD4 exome
AF:
AC:
1
AN:
1446998
Hom.:
Cov.:
27
AF XY:
AC XY:
0
AN XY:
719760
Gnomad4 AFR exome
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Gnomad4 AMR exome
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Gnomad4 ASJ exome
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Gnomad4 EAS exome
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Gnomad4 SAS exome
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Gnomad4 FIN exome
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Gnomad4 OTH exome
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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 26, 2021 | The c.1670A>G (p.K557R) alteration is located in exon 16 (coding exon 16) of the EXOC5 gene. This alteration results from a A to G substitution at nucleotide position 1670, causing the lysine (K) at amino acid position 557 to be replaced by an arginine (R). 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
T
BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Benign
T;T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
T
MetaRNN
Uncertain
D;D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.;.
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
Sift4G
Benign
T;T;T
Polyphen
P;.;D
Vest4
MutPred
Loss of methylation at K557 (P = 0.0159);.;.;
MVP
MPC
0.96
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
Publications
No publications associated with this variant yet.