chr14-57233864-T-G
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PP3_ModerateBS2
The NM_006544.4(EXOC5):c.734A>C(p.Asp245Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000122 in 1,610,780 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00013 ( 0 hom. )
Consequence
EXOC5
NM_006544.4 missense
NM_006544.4 missense
Scores
5
7
4
Clinical Significance
Conservation
PhyloP100: 7.91
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.
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.86
BS2
?
High AC in GnomAd at 10 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EXOC5 | NM_006544.4 | c.734A>C | p.Asp245Ala | missense_variant | 9/18 | ENST00000621441.5 | |
EXOC5 | XM_005267272.4 | c.848A>C | p.Asp283Ala | missense_variant | 9/18 | ||
EXOC5 | XM_047430882.1 | c.569A>C | p.Asp190Ala | missense_variant | 9/18 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EXOC5 | ENST00000621441.5 | c.734A>C | p.Asp245Ala | missense_variant | 9/18 | 1 | NM_006544.4 | P1 | |
EXOC5 | ENST00000340918.11 | c.539A>C | p.Asp180Ala | missense_variant | 8/17 | 2 | |||
EXOC5 | ENST00000556629.1 | n.344A>C | non_coding_transcript_exon_variant | 4/6 | 3 | ||||
EXOC5 | ENST00000555148.5 | c.*568A>C | 3_prime_UTR_variant, NMD_transcript_variant | 9/18 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000657 AC: 10AN: 152152Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000443 AC: 11AN: 248390Hom.: 0 AF XY: 0.0000520 AC XY: 7AN XY: 134726
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GnomAD4 exome AF: 0.000128 AC: 186AN: 1458628Hom.: 0 Cov.: 28 AF XY: 0.000114 AC XY: 83AN XY: 725788
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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 | Nov 18, 2022 | The c.734A>C (p.D245A) alteration is located in exon 9 (coding exon 9) of the EXOC5 gene. This alteration results from a A to C substitution at nucleotide position 734, causing the aspartic acid (D) at amino acid position 245 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Pathogenic
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T;T;T
Eigen
Uncertain
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.;.
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
Sift4G
Uncertain
D;D;D
Polyphen
D;.;D
Vest4
MVP
MPC
1.3
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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