chr14-57235745-A-C
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_006544.4(EXOC5):c.635T>G(p.Met212Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,118 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 0.0000066 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000043 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
EXOC5
NM_006544.4 missense
NM_006544.4 missense
Scores
10
5
1
Clinical Significance
Conservation
PhyloP100: 9.23
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 Likely_pathogenic. Variant got 6 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.94
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EXOC5 | NM_006544.4 | c.635T>G | p.Met212Arg | missense_variant | 7/18 | ENST00000621441.5 | |
EXOC5 | XM_005267272.4 | c.749T>G | p.Met250Arg | missense_variant | 7/18 | ||
EXOC5 | XM_047430882.1 | c.470T>G | p.Met157Arg | missense_variant | 7/18 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EXOC5 | ENST00000621441.5 | c.635T>G | p.Met212Arg | missense_variant | 7/18 | 1 | NM_006544.4 | P1 | |
EXOC5 | ENST00000340918.11 | c.440T>G | p.Met147Arg | missense_variant | 6/17 | 2 | |||
EXOC5 | ENST00000556629.1 | n.245T>G | non_coding_transcript_exon_variant | 2/6 | 3 | ||||
EXOC5 | ENST00000555148.5 | c.*469T>G | 3_prime_UTR_variant, NMD_transcript_variant | 7/18 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152118Hom.: 0 Cov.: 31
GnomAD3 genomes
?
AF:
AC:
1
AN:
152118
Hom.:
Cov.:
31
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0000116 AC: 2AN: 172606Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 90944
GnomAD3 exomes
AF:
AC:
2
AN:
172606
Hom.:
AF XY:
AC XY:
0
AN XY:
90944
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 Data not reliable, filtered out with message: AS_VQSR AF: 0.00000428 AC: 6AN: 1400952Hom.: 0 Cov.: 27 AF XY: 0.00000578 AC XY: 4AN XY: 692130
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
AC:
6
AN:
1400952
Hom.:
Cov.:
27
AF XY:
AC XY:
4
AN XY:
692130
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152118Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 74294
GnomAD4 genome
?
AF:
AC:
1
AN:
152118
Hom.:
Cov.:
31
AF XY:
AC XY:
0
AN XY:
74294
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Bravo
AF:
ExAC
?
AF:
AC:
2
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 | May 27, 2022 | The c.635T>G (p.M212R) alteration is located in exon 7 (coding exon 7) of the EXOC5 gene. This alteration results from a T to G substitution at nucleotide position 635, causing the methionine (M) at amino acid position 212 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
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Uncertain
D;D;D
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M;.;.
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
Sift4G
Pathogenic
D;D;D
Polyphen
D;.;D
Vest4
MutPred
Loss of stability (P = 0.0344);Loss of stability (P = 0.0344);.;
MVP
MPC
1.5
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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