14-57209616-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_006544.4(EXOC5):​c.1889T>C​(p.Leu630Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,232 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: not found (cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

EXOC5
NM_006544.4 missense

Scores

4
10
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.15
Variant links:
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 Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.773

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
EXOC5NM_006544.4 linkc.1889T>C p.Leu630Ser missense_variant Exon 17 of 18 ENST00000621441.5 NP_006535.1 O00471
EXOC5XM_005267272.4 linkc.2003T>C p.Leu668Ser missense_variant Exon 17 of 18 XP_005267329.1
EXOC5XM_047430882.1 linkc.1724T>C p.Leu575Ser missense_variant Exon 17 of 18 XP_047286838.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
EXOC5ENST00000621441.5 linkc.1889T>C p.Leu630Ser missense_variant Exon 17 of 18 1 NM_006544.4 ENSP00000484855.1 O00471

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1461232
Hom.:
0
Cov.:
31
AF XY:
0.00000275
AC XY:
2
AN XY:
726894
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000270
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Sep 10, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1889T>C (p.L630S) alteration is located in exon 17 (coding exon 17) of the EXOC5 gene. This alteration results from a T to C substitution at nucleotide position 1889, causing the leucine (L) at amino acid position 630 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.85
BayesDel_addAF
Pathogenic
0.25
D
BayesDel_noAF
Uncertain
0.12
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Benign
0.33
T;T;T
Eigen
Uncertain
0.40
Eigen_PC
Uncertain
0.49
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Uncertain
0.95
D;D;D
M_CAP
Benign
0.037
D
MetaRNN
Pathogenic
0.77
D;D;D
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
1.9
L;.;.
PrimateAI
Pathogenic
0.88
D
PROVEAN
Uncertain
-3.0
.;.;D
REVEL
Uncertain
0.41
Sift
Uncertain
0.0060
.;.;D
Sift4G
Uncertain
0.030
D;D;D
Polyphen
0.63
P;.;P
Vest4
0.94
MutPred
0.49
Loss of sheet (P = 0.0315);.;.;
MVP
0.72
MPC
1.2
ClinPred
0.97
D
GERP RS
5.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.31
gMVP
0.62

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1882765199; hg19: chr14-57676334; API