rs201102355

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_178516.4(EXOC3L1):​c.2147G>C​(p.Arg716Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000073 in 1,369,832 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 in silico tools predict a benign 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. R716H) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 7.3e-7 ( 0 hom. )

Consequence

EXOC3L1
NM_178516.4 missense

Scores

1
2
16

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.663
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
EXOC3L1NM_178516.4 linkc.2147G>C p.Arg716Pro missense_variant Exon 14 of 14 ENST00000314586.11 NP_848611.2 Q86VI1A0A024R6U6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
EXOC3L1ENST00000314586.11 linkc.2147G>C p.Arg716Pro missense_variant Exon 14 of 14 2 NM_178516.4 ENSP00000325674.6 Q86VI1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
7.30e-7
AC:
1
AN:
1369832
Hom.:
0
Cov.:
32
AF XY:
0.00000148
AC XY:
1
AN XY:
675846
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:
9.31e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.029
T
BayesDel_noAF
Benign
-0.28
CADD
Benign
19
DANN
Benign
0.83
DEOGEN2
Benign
0.0070
T
Eigen
Benign
0.17
Eigen_PC
Benign
0.13
FATHMM_MKL
Benign
0.51
D
LIST_S2
Benign
0.77
T
M_CAP
Benign
0.015
T
MetaRNN
Uncertain
0.50
D
MetaSVM
Benign
-1.1
T
MutationAssessor
Pathogenic
2.9
M
PrimateAI
Uncertain
0.60
T
PROVEAN
Benign
0.40
N
REVEL
Benign
0.18
Sift
Benign
0.18
T
Sift4G
Benign
0.24
T
Polyphen
0.88
P
Vest4
0.46
MutPred
0.63
Loss of helix (P = 0.0033);
MVP
0.67
MPC
1.2
ClinPred
0.98
D
GERP RS
4.4
Varity_R
0.24
gMVP
0.88

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-67218391; API