4-55868474-C-T
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_001024924.2(EXOC1):c.554C>T(p.Ala185Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,613,234 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: 32)
Exomes 𝑓: 0.000012 ( 0 hom. )
Consequence
EXOC1
NM_001024924.2 missense
NM_001024924.2 missense
Scores
6
8
4
Clinical Significance
Conservation
PhyloP100: 7.48
Genes affected
EXOC1 (HGNC:30380): (exocyst complex component 1) 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 the 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. Alternatively spliced transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Jul 2008]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.938
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EXOC1 | NM_001024924.2 | c.554C>T | p.Ala185Val | missense_variant | 5/19 | ENST00000381295.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EXOC1 | ENST00000381295.7 | c.554C>T | p.Ala185Val | missense_variant | 5/19 | 1 | NM_001024924.2 | A1 | |
EXOC1 | ENST00000346134.11 | c.554C>T | p.Ala185Val | missense_variant | 5/19 | 2 | A1 | ||
EXOC1 | ENST00000349598.6 | c.554C>T | p.Ala185Val | missense_variant | 5/18 | 2 | P3 | ||
EXOC1 | ENST00000505501.1 | n.539C>T | non_coding_transcript_exon_variant | 4/4 | 3 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 151970Hom.: 0 Cov.: 32
GnomAD3 genomes
AF:
AC:
1
AN:
151970
Hom.:
Cov.:
32
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: 0.0000239 AC: 6AN: 251110Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135712
GnomAD3 exomes
AF:
AC:
6
AN:
251110
Hom.:
AF XY:
AC XY:
4
AN XY:
135712
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 AF: 0.0000123 AC: 18AN: 1461264Hom.: 0 Cov.: 30 AF XY: 0.0000110 AC XY: 8AN XY: 726954
GnomAD4 exome
AF:
AC:
18
AN:
1461264
Hom.:
Cov.:
30
AF XY:
AC XY:
8
AN XY:
726954
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: 0.00000658 AC: 1AN: 151970Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74190
GnomAD4 genome
AF:
AC:
1
AN:
151970
Hom.:
Cov.:
32
AF XY:
AC XY:
0
AN XY:
74190
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:
3
Asia WGS
AF:
AC:
1
AN:
3478
EpiCase
AF:
EpiControl
AF:
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 | Jun 01, 2023 | The c.554C>T (p.A185V) alteration is located in exon 5 (coding exon 4) of the EXOC1 gene. This alteration results from a C to T substitution at nucleotide position 554, causing the alanine (A) at amino acid position 185 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
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
T;T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
M_CAP
Benign
T
MetaRNN
Pathogenic
D;D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;M
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D
REVEL
Uncertain
Sift
Uncertain
D;D;D
Sift4G
Uncertain
D;D;D
Polyphen
D;D;D
Vest4
MutPred
Gain of catalytic residue at A185 (P = 0.0626);Gain of catalytic residue at A185 (P = 0.0626);Gain of catalytic residue at A185 (P = 0.0626);
MVP
MPC
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