chr14-57208758-G-C
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_006544.4(EXOC5):c.1978C>G(p.Leu660Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000342 in 1,609,064 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000034 ( 0 hom. )
Consequence
EXOC5
NM_006544.4 missense
NM_006544.4 missense
Scores
8
4
4
Clinical Significance
Conservation
PhyloP100: 10.0
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 -4 ACMG points.
BS2
?
High AC in GnomAd at 5 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EXOC5 | NM_006544.4 | c.1978C>G | p.Leu660Val | missense_variant | 18/18 | ENST00000621441.5 | |
EXOC5 | XM_005267272.4 | c.2092C>G | p.Leu698Val | missense_variant | 18/18 | ||
EXOC5 | XM_047430882.1 | c.1813C>G | p.Leu605Val | missense_variant | 18/18 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EXOC5 | ENST00000621441.5 | c.1978C>G | p.Leu660Val | missense_variant | 18/18 | 1 | NM_006544.4 | P1 | |
EXOC5 | ENST00000554011.5 | n.1697C>G | non_coding_transcript_exon_variant | 8/8 | 1 | ||||
EXOC5 | ENST00000340918.11 | c.1783C>G | p.Leu595Val | missense_variant | 17/17 | 2 | |||
EXOC5 | ENST00000555148.5 | c.*1812C>G | 3_prime_UTR_variant, NMD_transcript_variant | 18/18 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152152Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000162 AC: 4AN: 246430Hom.: 0 AF XY: 0.00000747 AC XY: 1AN XY: 133882
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GnomAD4 exome AF: 0.0000343 AC: 50AN: 1456794Hom.: 0 Cov.: 28 AF XY: 0.0000373 AC XY: 27AN XY: 724304
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GnomAD4 genome ? AF: 0.0000328 AC: 5AN: 152270Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74452
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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 | Jan 10, 2023 | The c.1978C>G (p.L660V) alteration is located in exon 18 (coding exon 18) of the EXOC5 gene. This alteration results from a C to G substitution at nucleotide position 1978, causing the leucine (L) at amino acid position 660 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
Uncertain
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Benign
T;T;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.;.
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
Sift4G
Pathogenic
D;D;D
Polyphen
D;.;D
Vest4
MutPred
Loss of stability (P = 0.1695);.;.;
MVP
MPC
1.2
ClinPred
D
GERP RS
Varity_R
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