chr19-14397699-T-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_078481.4(ADGRE5):c.667T>A(p.Ser223Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 19)
Consequence
ADGRE5
NM_078481.4 missense
NM_078481.4 missense
Scores
1
16
Clinical Significance
Conservation
PhyloP100: 0.841
Genes affected
ADGRE5 (HGNC:1711): (adhesion G protein-coupled receptor E5) This gene encodes a member of the EGF-TM7 subfamily of adhesion G protein-coupled receptors, which mediate cell-cell interactions. These proteins are cleaved by self-catalytic proteolysis into a large extracellular subunit and seven-span transmembrane subunit, which associate at the cell surface as a receptor complex. The encoded protein may play a role in cell adhesion as well as leukocyte recruitment, activation and migration, and contains multiple extracellular EGF-like repeats which mediate binding to chondroitin sulfate and the cell surface complement regulatory protein CD55. Expression of this gene may play a role in the progression of several types of cancer. Alternatively spliced transcript variants encoding multiple isoforms with 3 to 5 EGF-like repeats have been observed for this gene. This gene is found in a cluster with other EGF-TM7 genes on the short arm of chromosome 19. [provided by RefSeq, Jun 2011]
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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/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ADGRE5 | NM_078481.4 | c.667T>A | p.Ser223Thr | missense_variant | 7/20 | ENST00000242786.6 | |
ADGRE5 | NM_001025160.3 | c.520T>A | p.Ser174Thr | missense_variant | 6/19 | ||
ADGRE5 | NM_001784.6 | c.388T>A | p.Ser130Thr | missense_variant | 5/18 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ADGRE5 | ENST00000242786.6 | c.667T>A | p.Ser223Thr | missense_variant | 7/20 | 1 | NM_078481.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 19
GnomAD3 genomes
?
Cov.:
19
GnomAD4 exome Cov.: 24
GnomAD4 exome
Cov.:
24
GnomAD4 genome ? Cov.: 19
GnomAD4 genome
?
Cov.:
19
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 | Oct 06, 2021 | The c.667T>A (p.S223T) alteration is located in exon 7 (coding exon 7) of the ADGRE5 gene. This alteration results from a T to A substitution at nucleotide position 667, causing the serine (S) at amino acid position 223 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T;T;T
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D;D
MetaSVM
Benign
T
MutationTaster
Benign
N;N;N
PrimateAI
Benign
T
PROVEAN
Benign
N;.;N;N
REVEL
Benign
Sift
Benign
T;.;T;T
Sift4G
Benign
T;T;T;T
Vest4
MutPred
0.86
.;.;.;Loss of sheet (P = 0.1158);
MVP
MPC
2.0
ClinPred
T
GERP RS
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
Publications
No publications associated with this variant yet.