rs1396089145

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_178516.4(EXOC3L1):​c.1883T>G​(p.Leu628Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L628P) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Consequence

EXOC3L1
NM_178516.4 missense

Scores

5
9
5

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.31
Variant links:
Genes affected
EXOC3L1 (HGNC:27540): (exocyst complex component 3 like 1) Predicted to enable SNARE binding activity. Predicted to be involved in exocyst localization; exocytosis; and peptide hormone secretion. Predicted to be located in secretory granule. Predicted to be part of exocyst. [provided by Alliance of Genome Resources, Apr 2022]

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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, 0.963

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
EXOC3L1NM_178516.4 linkc.1883T>G p.Leu628Arg missense_variant Exon 12 of 14 ENST00000314586.11 NP_848611.2 Q86VI1A0A024R6U6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
EXOC3L1ENST00000314586.11 linkc.1883T>G p.Leu628Arg missense_variant Exon 12 of 14 2 NM_178516.4 ENSP00000325674.6 Q86VI1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
33
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.79
BayesDel_addAF
Pathogenic
0.21
D
BayesDel_noAF
Uncertain
0.070
CADD
Pathogenic
28
DANN
Uncertain
1.0
DEOGEN2
Benign
0.10
T;.;.
Eigen
Uncertain
0.60
Eigen_PC
Uncertain
0.53
FATHMM_MKL
Uncertain
0.88
D
LIST_S2
Benign
0.74
T;T;T
M_CAP
Benign
0.025
T
MetaRNN
Pathogenic
0.96
D;D;D
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.8
M;.;.
PrimateAI
Uncertain
0.69
T
PROVEAN
Pathogenic
-4.8
D;D;D
REVEL
Uncertain
0.49
Sift
Uncertain
0.0010
D;D;D
Sift4G
Pathogenic
0.0
D;.;D
Polyphen
1.0
D;D;.
Vest4
0.86
MutPred
0.91
Gain of disorder (P = 0.0174);.;.;
MVP
0.64
MPC
2.4
ClinPred
1.0
D
GERP RS
4.8
Varity_R
0.87
gMVP
0.89

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
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: rs1396089145; hg19: chr16-67218827; API